ChloroquineV1, Ncbi, Merge, bibRecord, 000347

Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression.

Identifieur interne : 000347 ( Ncbi/Merge ); précédent : 000346; suivant : 000348

Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression.

Auteurs : Wen Cai Zhang [Singapour] ; Tan Min Chin [Singapour] ; Henry Yang [Singapour] ; Min En Nga [Singapour] ; Declan Patrick Lunny [Singapour] ; Edwin Kok Hao Lim [Singapour] ; Li Li Sun [Singapour] ; Yin Huei Pang [Singapour] ; Yi Ning Leow [Singapour] ; Shanneen Rossellini Y. Malusay [Singapour] ; Priscilla Xin Hui Lim [Singapour] ; Jeravan Zili Lee [Singapour] ; Benedict Jian Wei Tan [Singapour] ; Ng Shyh-Chang [Singapour] ; Elaine Hsuen Lim [Singapour] ; Wan Teck Lim [Singapour] ; Daniel Shao Weng Tan [Singapour] ; Eng Huat Tan [Singapour] ; Bee Choo Tai [Singapour] ; Ross Andrew Soo [Singapour] ; Wai Leong Tam [Singapour] ; Bing Lim [Singapour]

Source :

Nature communications [ 2041-1723 ] ; 2016.

RBID : pubmed:27325363

Descripteurs français

English descriptors

KwdEn :
- A549 Cells, Animals, Antineoplastic Combined Chemotherapy Protocols (pharmacology), Carcinoma, Non-Small-Cell Lung (genetics), Carcinoma, Non-Small-Cell Lung (metabolism), Carcinoma, Non-Small-Cell Lung (pathology), Carcinoma, Non-Small-Cell Lung (therapy), Disease Progression, Female, Gefitinib, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Hydroxychloroquine (pharmacology), Lung Neoplasms (genetics), Lung Neoplasms (metabolism), Lung Neoplasms (pathology), Lung Neoplasms (therapy), Lymphatic Metastasis, Mice, MicroRNAs (antagonists & inhibitors), MicroRNAs (genetics), MicroRNAs (metabolism), Neoplastic Stem Cells (metabolism), Neoplastic Stem Cells (pathology), Oligonucleotides (administration & dosage), Oligonucleotides (genetics), Oligonucleotides (metabolism), Quinazolines (pharmacology), Signal Transduction, Survival Analysis, Tumor Burden, Xenograft Model Antitumor Assays.
MESH :
- chemical , administration & dosage : Oligonucleotides.
- chemical , antagonists & inhibitors : MicroRNAs.
- chemical , genetics : MicroRNAs, Oligonucleotides.
- chemical , metabolism : MicroRNAs, Oligonucleotides.
- chemical , pharmacology : Hydroxychloroquine, Quinazolines.
- chemical : Gefitinib.
- genetics : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- metabolism : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Neoplastic Stem Cells.
- pathology : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Neoplastic Stem Cells.
- pharmacology : Antineoplastic Combined Chemotherapy Protocols.
- therapy : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- A549 Cells, Animals, Disease Progression, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Lymphatic Metastasis, Mice, Signal Transduction, Survival Analysis, Tumor Burden, Xenograft Model Antitumor Assays.

Abstract

The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, and may contribute towards tumour heterogeneity and TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumour-initiating potential of TICs and their ability to metastasize. Longitudinal analyses of serum miR-1246 and miR-1290 levels across time correlate their circulating levels to the clinical response of lung cancer patients who were receiving ongoing anti-neoplastic therapies. Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumours, thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.

DOI: 10.1038/ncomms11702
PubMed: 27325363

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Le document en format XML

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<author><name sortKey="Sun, Li Li" sort="Sun, Li Li" uniqKey="Sun L" first="Li Li" last="Sun">Li Li Sun</name>
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<author><name sortKey="Pang, Yin Huei" sort="Pang, Yin Huei" uniqKey="Pang Y" first="Yin Huei" last="Pang">Yin Huei Pang</name>
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<author><name sortKey="Leow, Yi Ning" sort="Leow, Yi Ning" uniqKey="Leow Y" first="Yi Ning" last="Leow">Yi Ning Leow</name>
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<author><name sortKey="Malusay, Shanneen Rossellini Y" sort="Malusay, Shanneen Rossellini Y" uniqKey="Malusay S" first="Shanneen Rossellini Y" last="Malusay">Shanneen Rossellini Y. Malusay</name>
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<author><name sortKey="Lim, Priscilla Xin Hui" sort="Lim, Priscilla Xin Hui" uniqKey="Lim P" first="Priscilla Xin Hui" last="Lim">Priscilla Xin Hui Lim</name>
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<author><name sortKey="Lee, Jeravan Zili" sort="Lee, Jeravan Zili" uniqKey="Lee J" first="Jeravan Zili" last="Lee">Jeravan Zili Lee</name>
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<author><name sortKey="Lim, Elaine Hsuen" sort="Lim, Elaine Hsuen" uniqKey="Lim E" first="Elaine Hsuen" last="Lim">Elaine Hsuen Lim</name>
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<author><name sortKey="Lim, Wan Teck" sort="Lim, Wan Teck" uniqKey="Lim W" first="Wan Teck" last="Lim">Wan Teck Lim</name>
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<author><name sortKey="Tan, Daniel Shao Weng" sort="Tan, Daniel Shao Weng" uniqKey="Tan D" first="Daniel Shao Weng" last="Tan">Daniel Shao Weng Tan</name>
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<author><name sortKey="Tan, Eng Huat" sort="Tan, Eng Huat" uniqKey="Tan E" first="Eng Huat" last="Tan">Eng Huat Tan</name>
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<author><name sortKey="Tai, Bee Choo" sort="Tai, Bee Choo" uniqKey="Tai B" first="Bee Choo" last="Tai">Bee Choo Tai</name>
<affiliation wicri:level="4"><nlm:affiliation>Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore.</nlm:affiliation>
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<author><name sortKey="Soo, Ross Andrew" sort="Soo, Ross Andrew" uniqKey="Soo R" first="Ross Andrew" last="Soo">Ross Andrew Soo</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression.</title>
<author><name sortKey="Zhang, Wen Cai" sort="Zhang, Wen Cai" uniqKey="Zhang W" first="Wen Cai" last="Zhang">Wen Cai Zhang</name>
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<author><name sortKey="Chin, Tan Min" sort="Chin, Tan Min" uniqKey="Chin T" first="Tan Min" last="Chin">Tan Min Chin</name>
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<author><name sortKey="Yang, Henry" sort="Yang, Henry" uniqKey="Yang H" first="Henry" last="Yang">Henry Yang</name>
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<author><name sortKey="Nga, Min En" sort="Nga, Min En" uniqKey="Nga M" first="Min En" last="Nga">Min En Nga</name>
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<wicri:regionArea>Department of Pathology, National University Hospital, Singapore 119074</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Lunny, Declan Patrick" sort="Lunny, Declan Patrick" uniqKey="Lunny D" first="Declan Patrick" last="Lunny">Declan Patrick Lunny</name>
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<wicri:regionArea>Institute of Medical Biology, Singapore 138648</wicri:regionArea>
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</affiliation>
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<author><name sortKey="Lim, Edwin Kok Hao" sort="Lim, Edwin Kok Hao" uniqKey="Lim E" first="Edwin Kok Hao" last="Lim">Edwin Kok Hao Lim</name>
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<country xml:lang="fr">Singapour</country>
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</affiliation>
</author>
<author><name sortKey="Sun, Li Li" sort="Sun, Li Li" uniqKey="Sun L" first="Li Li" last="Sun">Li Li Sun</name>
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<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Pang, Yin Huei" sort="Pang, Yin Huei" uniqKey="Pang Y" first="Yin Huei" last="Pang">Yin Huei Pang</name>
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</affiliation>
</author>
<author><name sortKey="Leow, Yi Ning" sort="Leow, Yi Ning" uniqKey="Leow Y" first="Yi Ning" last="Leow">Yi Ning Leow</name>
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<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
<wicri:noRegion>Singapore 138672</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Malusay, Shanneen Rossellini Y" sort="Malusay, Shanneen Rossellini Y" uniqKey="Malusay S" first="Shanneen Rossellini Y" last="Malusay">Shanneen Rossellini Y. Malusay</name>
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<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
<wicri:noRegion>Singapore 138672</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lim, Priscilla Xin Hui" sort="Lim, Priscilla Xin Hui" uniqKey="Lim P" first="Priscilla Xin Hui" last="Lim">Priscilla Xin Hui Lim</name>
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<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
<wicri:noRegion>Singapore 138672</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lee, Jeravan Zili" sort="Lee, Jeravan Zili" uniqKey="Lee J" first="Jeravan Zili" last="Lee">Jeravan Zili Lee</name>
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<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
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</author>
<author><name sortKey="Tan, Benedict Jian Wei" sort="Tan, Benedict Jian Wei" uniqKey="Tan B" first="Benedict Jian Wei" last="Tan">Benedict Jian Wei Tan</name>
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<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
<wicri:noRegion>Singapore 138672</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Shyh Chang, Ng" sort="Shyh Chang, Ng" uniqKey="Shyh Chang N" first="Ng" last="Shyh-Chang">Ng Shyh-Chang</name>
<affiliation wicri:level="1"><nlm:affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
<wicri:noRegion>Singapore 138672</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lim, Elaine Hsuen" sort="Lim, Elaine Hsuen" uniqKey="Lim E" first="Elaine Hsuen" last="Lim">Elaine Hsuen Lim</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Respiratory Medicine, Tan Tock Seng Hospital, Singapore 308433, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Respiratory Medicine, Tan Tock Seng Hospital, Singapore 308433</wicri:regionArea>
<wicri:noRegion>Singapore 308433</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lim, Wan Teck" sort="Lim, Wan Teck" uniqKey="Lim W" first="Wan Teck" last="Lim">Wan Teck Lim</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610</wicri:regionArea>
<wicri:noRegion>Singapore 169610</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tan, Daniel Shao Weng" sort="Tan, Daniel Shao Weng" uniqKey="Tan D" first="Daniel Shao Weng" last="Tan">Daniel Shao Weng Tan</name>
<affiliation wicri:level="1"><nlm:affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
<wicri:noRegion>Singapore 138672</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tan, Eng Huat" sort="Tan, Eng Huat" uniqKey="Tan E" first="Eng Huat" last="Tan">Eng Huat Tan</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610</wicri:regionArea>
<wicri:noRegion>Singapore 169610</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tai, Bee Choo" sort="Tai, Bee Choo" uniqKey="Tai B" first="Bee Choo" last="Tai">Bee Choo Tai</name>
<affiliation wicri:level="4"><nlm:affiliation>Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
</author>
<author><name sortKey="Soo, Ross Andrew" sort="Soo, Ross Andrew" uniqKey="Soo R" first="Ross Andrew" last="Soo">Ross Andrew Soo</name>
<affiliation wicri:level="4"><nlm:affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
</author>
<author><name sortKey="Tam, Wai Leong" sort="Tam, Wai Leong" uniqKey="Tam W" first="Wai Leong" last="Tam">Wai Leong Tam</name>
<affiliation wicri:level="1"><nlm:affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
<wicri:noRegion>Singapore 138672</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lim, Bing" sort="Lim, Bing" uniqKey="Lim B" first="Bing" last="Lim">Bing Lim</name>
<affiliation wicri:level="1"><nlm:affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Genome Institute of Singapore, Singapore 138672</wicri:regionArea>
<wicri:noRegion>Singapore 138672</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>A549 Cells</term>
<term>Animals</term>
<term>Antineoplastic Combined Chemotherapy Protocols (pharmacology)</term>
<term>Carcinoma, Non-Small-Cell Lung (genetics)</term>
<term>Carcinoma, Non-Small-Cell Lung (metabolism)</term>
<term>Carcinoma, Non-Small-Cell Lung (pathology)</term>
<term>Carcinoma, Non-Small-Cell Lung (therapy)</term>
<term>Disease Progression</term>
<term>Female</term>
<term>Gefitinib</term>
<term>Gene Expression Regulation, Neoplastic</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Hydroxychloroquine (pharmacology)</term>
<term>Lung Neoplasms (genetics)</term>
<term>Lung Neoplasms (metabolism)</term>
<term>Lung Neoplasms (pathology)</term>
<term>Lung Neoplasms (therapy)</term>
<term>Lymphatic Metastasis</term>
<term>Mice</term>
<term>MicroRNAs (antagonists & inhibitors)</term>
<term>MicroRNAs (genetics)</term>
<term>MicroRNAs (metabolism)</term>
<term>Neoplastic Stem Cells (metabolism)</term>
<term>Neoplastic Stem Cells (pathology)</term>
<term>Oligonucleotides (administration & dosage)</term>
<term>Oligonucleotides (genetics)</term>
<term>Oligonucleotides (metabolism)</term>
<term>Quinazolines (pharmacology)</term>
<term>Signal Transduction</term>
<term>Survival Analysis</term>
<term>Tumor Burden</term>
<term>Xenograft Model Antitumor Assays</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de survie</term>
<term>Animaux</term>
<term>Carcinome pulmonaire non à petites cellules ()</term>
<term>Carcinome pulmonaire non à petites cellules (anatomopathologie)</term>
<term>Carcinome pulmonaire non à petites cellules (génétique)</term>
<term>Carcinome pulmonaire non à petites cellules (métabolisme)</term>
<term>Cellules A549</term>
<term>Cellules HEK293</term>
<term>Cellules souches tumorales (anatomopathologie)</term>
<term>Cellules souches tumorales (métabolisme)</term>
<term>Charge tumorale</term>
<term>Femelle</term>
<term>Humains</term>
<term>Hydroxychloroquine (pharmacologie)</term>
<term>Métastase lymphatique</term>
<term>Oligonucléotides (administration et posologie)</term>
<term>Oligonucléotides (génétique)</term>
<term>Oligonucléotides (métabolisme)</term>
<term>Protocoles de polychimiothérapie antinéoplasique (pharmacologie)</term>
<term>Quinazolines (pharmacologie)</term>
<term>Régulation de l'expression des gènes tumoraux</term>
<term>Souris</term>
<term>Tests d'activité antitumorale sur modèle de xénogreffe</term>
<term>Transduction du signal</term>
<term>Tumeurs du poumon ()</term>
<term>Tumeurs du poumon (anatomopathologie)</term>
<term>Tumeurs du poumon (génétique)</term>
<term>Tumeurs du poumon (métabolisme)</term>
<term>microARN (antagonistes et inhibiteurs)</term>
<term>microARN (génétique)</term>
<term>microARN (métabolisme)</term>
<term>Évolution de la maladie</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Oligonucleotides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>MicroRNAs</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>MicroRNAs</term>
<term>Oligonucleotides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>MicroRNAs</term>
<term>Oligonucleotides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Hydroxychloroquine</term>
<term>Quinazolines</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Gefitinib</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Oligonucléotides</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term>
<term>Cellules souches tumorales</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>microARN</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term>
<term>Lung Neoplasms</term>
</keywords>
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<term>Oligonucléotides</term>
<term>Tumeurs du poumon</term>
<term>microARN</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term>
<term>Lung Neoplasms</term>
<term>Neoplastic Stem Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term>
<term>Cellules souches tumorales</term>
<term>Oligonucléotides</term>
<term>Tumeurs du poumon</term>
<term>microARN</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term>
<term>Lung Neoplasms</term>
<term>Neoplastic Stem Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Hydroxychloroquine</term>
<term>Protocoles de polychimiothérapie antinéoplasique</term>
<term>Quinazolines</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term>
</keywords>
<keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>A549 Cells</term>
<term>Animals</term>
<term>Disease Progression</term>
<term>Female</term>
<term>Gene Expression Regulation, Neoplastic</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Lymphatic Metastasis</term>
<term>Mice</term>
<term>Signal Transduction</term>
<term>Survival Analysis</term>
<term>Tumor Burden</term>
<term>Xenograft Model Antitumor Assays</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term>
<term>Animaux</term>
<term>Carcinome pulmonaire non à petites cellules</term>
<term>Cellules A549</term>
<term>Cellules HEK293</term>
<term>Charge tumorale</term>
<term>Femelle</term>
<term>Humains</term>
<term>Métastase lymphatique</term>
<term>Régulation de l'expression des gènes tumoraux</term>
<term>Souris</term>
<term>Tests d'activité antitumorale sur modèle de xénogreffe</term>
<term>Transduction du signal</term>
<term>Tumeurs du poumon</term>
<term>Évolution de la maladie</term>
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<front><div type="abstract" xml:lang="en">The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, and may contribute towards tumour heterogeneity and TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumour-initiating potential of TICs and their ability to metastasize. Longitudinal analyses of serum miR-1246 and miR-1290 levels across time correlate their circulating levels to the clinical response of lung cancer patients who were receiving ongoing anti-neoplastic therapies. Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumours, thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27325363</PMID>
<DateCompleted><Year>2018</Year>
<Month>08</Month>
<Day>21</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>12</Month>
<Day>02</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>7</Volume>
<PubDate><Year>2016</Year>
<Month>06</Month>
<Day>21</Day>
</PubDate>
</JournalIssue>
<Title>Nature communications</Title>
<ISOAbbreviation>Nat Commun</ISOAbbreviation>
</Journal>
<ArticleTitle>Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression.</ArticleTitle>
<Pagination><MedlinePgn>11702</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/ncomms11702</ELocationID>
<Abstract><AbstractText>The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, and may contribute towards tumour heterogeneity and TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumour-initiating potential of TICs and their ability to metastasize. Longitudinal analyses of serum miR-1246 and miR-1290 levels across time correlate their circulating levels to the clinical response of lung cancer patients who were receiving ongoing anti-neoplastic therapies. Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumours, thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Wen Cai</ForeName>
<Initials>WC</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chin</LastName>
<ForeName>Tan Min</ForeName>
<Initials>TM</Initials>
<AffiliationInfo><Affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Haematology-Oncology, National University Cancer Institute, Singapore 119074, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yang</LastName>
<ForeName>Henry</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nga</LastName>
<ForeName>Min En</ForeName>
<Initials>ME</Initials>
<AffiliationInfo><Affiliation>Department of Pathology, National University Hospital, Singapore 119074, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lunny</LastName>
<ForeName>Declan Patrick</ForeName>
<Initials>DP</Initials>
<AffiliationInfo><Affiliation>Institute of Medical Biology, Singapore 138648, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lim</LastName>
<ForeName>Edwin Kok Hao</ForeName>
<Initials>EK</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sun</LastName>
<ForeName>Li Li</ForeName>
<Initials>LL</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pang</LastName>
<ForeName>Yin Huei</ForeName>
<Initials>YH</Initials>
<AffiliationInfo><Affiliation>Department of Pathology, National University Hospital, Singapore 119074, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Leow</LastName>
<ForeName>Yi Ning</ForeName>
<Initials>YN</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Malusay</LastName>
<ForeName>Shanneen Rossellini Y</ForeName>
<Initials>SR</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lim</LastName>
<ForeName>Priscilla Xin Hui</ForeName>
<Initials>PX</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lee</LastName>
<ForeName>Jeravan Zili</ForeName>
<Initials>JZ</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tan</LastName>
<ForeName>Benedict Jian Wei</ForeName>
<Initials>BJ</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Shyh-Chang</LastName>
<ForeName>Ng</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lim</LastName>
<ForeName>Elaine Hsuen</ForeName>
<Initials>EH</Initials>
<AffiliationInfo><Affiliation>Department of Respiratory Medicine, Tan Tock Seng Hospital, Singapore 308433, Singapore.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lim</LastName>
<ForeName>Wan Teck</ForeName>
<Initials>WT</Initials>
<AffiliationInfo><Affiliation>Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tan</LastName>
<ForeName>Daniel Shao Weng</ForeName>
<Initials>DS</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tan</LastName>
<ForeName>Eng Huat</ForeName>
<Initials>EH</Initials>
<AffiliationInfo><Affiliation>Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tai</LastName>
<ForeName>Bee Choo</ForeName>
<Initials>BC</Initials>
<AffiliationInfo><Affiliation>Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Soo</LastName>
<ForeName>Ross Andrew</ForeName>
<Initials>RA</Initials>
<AffiliationInfo><Affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Haematology-Oncology, National University Cancer Institute, Singapore 119074, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tam</LastName>
<ForeName>Wai Leong</ForeName>
<Initials>WL</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lim</LastName>
<ForeName>Bing</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Genome Institute of Singapore, Singapore 138672, Singapore.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2016</Year>
<Month>06</Month>
<Day>21</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Nat Commun</MedlineTA>
<NlmUniqueID>101528555</NlmUniqueID>
<ISSNLinking>2041-1723</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C577700">MIRN1246 microRNA, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C574604">MIRN1290 microRNA, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D035683">MicroRNAs</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D009841">Oligonucleotides</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011799">Quinazolines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C477371">locked nucleic acid</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber>
<NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>S65743JHBS</RegistryNumber>
<NameOfSubstance UI="D000077156">Gefitinib</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000072283" MajorTopicYN="N">A549 Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000971" MajorTopicYN="N">Antineoplastic Combined Chemotherapy Protocols</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002289" MajorTopicYN="N">Carcinoma, Non-Small-Cell Lung</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018450" MajorTopicYN="N">Disease Progression</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000077156" MajorTopicYN="N">Gefitinib</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015972" MajorTopicYN="Y">Gene Expression Regulation, Neoplastic</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008175" MajorTopicYN="N">Lung Neoplasms</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008207" MajorTopicYN="N">Lymphatic Metastasis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D035683" MajorTopicYN="N">MicroRNAs</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014411" MajorTopicYN="N">Neoplastic Stem Cells</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009841" MajorTopicYN="N">Oligonucleotides</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011799" MajorTopicYN="N">Quinazolines</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016019" MajorTopicYN="N">Survival Analysis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D047368" MajorTopicYN="N">Tumor Burden</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D023041" MajorTopicYN="N">Xenograft Model Antitumor Assays</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year>
<Month>08</Month>
<Day>04</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2016</Year>
<Month>04</Month>
<Day>18</Day>
</PubMedPubDate>
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Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression.

Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression.

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