ChloroquineV1, Main, Exploration, bibRecord, 000186

Circular RNA circHIPK3 modulates autophagy via MIR124-3p-STAT3-PRKAA/AMPKα signaling in STK11 mutant lung cancer.

Identifieur interne : 000186 ( Main/Exploration ); précédent : 000185; suivant : 000187

Circular RNA circHIPK3 modulates autophagy via MIR124-3p-STAT3-PRKAA/AMPKα signaling in STK11 mutant lung cancer.

Auteurs : Xiuyuan Chen [République populaire de Chine] ; Rui Mao [République populaire de Chine] ; Wenmei Su [République populaire de Chine] ; Xia Yang [République populaire de Chine] ; Qianqian Geng [République populaire de Chine] ; Chunfang Guo [États-Unis] ; Zhuwen Wang [États-Unis] ; Jun Wang [République populaire de Chine] ; Laura A. Kresty [États-Unis] ; David G. Beer [États-Unis] ; Andrew C. Chang [États-Unis] ; Guoan Chen [République populaire de Chine]

Source :

Autophagy [ 1554-8635 ] ; 2020.

RBID : pubmed:31232177

Abstract

The role of circular RNA in cancer is emerging. A newly reported circular RNA HIPK3 (circHIPK3) is critical in cell proliferation of various cancer types, although its role in non-small cell lung cancer (NSCLC), has yet to be elucidated. Our results provided evidence that silencing of circHIPK3 significantly impaired cell proliferation, migration, invasion and induced macroautophagy/autophagy. Mechanistically, we uncovered that autophagy was induced upon loss of circHIPK3 via the MIR124-3p-STAT3-PRKAA/AMPKa axis in STK11 mutant lung cancer cell lines (A549 and H838). STAT3 abrogation as well as transfection with a MIR124-3p mimic, recapitulated the induction of autophagy. We also demonstrated antagonistic regulation on autophagy between circHIPK3 and linear HIPK3 (linHIPK3). We therefore propose that the ratio between circHIPK3 and linHIPK3 (C:L ratio) may reflect autophagy levels in cancer cells. We observed that a high C:L ratio (>0.49) was an indicator of poor survival, especially in advanced-stage NSCLC patients. These results support that circHIPK3 is a key autophagy regulator in a subset of lung cancer and has potential clinical use as a prognostic factor. The circular RNA HIPK3 (circHIPK3) functions as an oncogene and autophagy regulator may potential use as a prognostic marker and therapeutic target in lung cancer.Abbreviations 3-MA: 3-methyladenine; AMPK: AMP-activated protein kinase; ATG7: autophagy related 7; Baf-A: bafilomycin A₁; BECN1: beclin 1; circHIPK3: circular HIPK3; CQ: chloroquine; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HIPK3: homeodomain interacting protein kinase 3; IL6R: interleukin 6 receptor; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; NSCLC: non-small cell lung cancer; RFP: red fluorescent protein; RPS6KB1/S6K: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; STAT3: signal transducer and activator of transcription 3; STK11: serine/threonine kinase 11.

DOI: 10.1080/15548627.2019.1634945
PubMed: 31232177

Affiliations:

Le document en format XML

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 modulates autophagy via <i>MIR124-3p</i>
-STAT3-PRKAA/AMPKα signaling in STK11 mutant lung cancer.</title>
<author><name sortKey="Chen, Xiuyuan" sort="Chen, Xiuyuan" uniqKey="Chen X" first="Xiuyuan" last="Chen">Xiuyuan Chen</name>
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<front><div type="abstract" xml:lang="en">The role of circular RNA in cancer is emerging. A newly reported circular RNA <i>HIPK3</i>
 (<i>circHIPK3)</i>
 is critical in cell proliferation of various cancer types, although its role in non-small cell lung cancer (NSCLC), has yet to be elucidated. Our results provided evidence that silencing of <i>circHIPK3</i>
 significantly impaired cell proliferation, migration, invasion and induced macroautophagy/autophagy. Mechanistically, we uncovered that autophagy was induced upon loss of <i>circHIPK3</i>
 via the <i>MIR124-3p</i>
-STAT3-PRKAA/AMPKa axis in STK11 mutant lung cancer cell lines (A549 and H838). STAT3 abrogation as well as transfection with a <i>MIR124-3p</i>
 mimic, recapitulated the induction of autophagy. We also demonstrated antagonistic regulation on autophagy between <i>circHIPK3</i>
 and linear <i>HIPK3</i>
 (<i>linHIPK3</i>
). We therefore propose that the ratio between <i>circHIPK3</i>
 and <i>linHIPK3</i>
 (C:L ratio) may reflect autophagy levels in cancer cells. We observed that a high C:L ratio (>0.49) was an indicator of poor survival, especially in advanced-stage NSCLC patients. These results support that <i>circHIPK3</i>
 is a key autophagy regulator in a subset of lung cancer and has potential clinical use as a prognostic factor. The circular RNA <i>HIPK3</i>
 (<i>circHIPK3)</i>
 functions as an oncogene and autophagy regulator may potential use as a prognostic marker and therapeutic target in lung cancer.<b>Abbreviations</b>
 3-MA: 3-methyladenine; AMPK: AMP-activated protein kinase; ATG7: autophagy related 7; Baf-A: bafilomycin A<sub>1</sub>
; BECN1: beclin 1; <i>circHIPK3</i>
: circular HIPK3; CQ: chloroquine; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HIPK3: homeodomain interacting protein kinase 3; IL6R: interleukin 6 receptor; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; NSCLC: non-small cell lung cancer; RFP: red fluorescent protein; RPS6KB1/S6K: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; STAT3: signal transducer and activator of transcription 3; STK11: serine/threonine kinase 11.</div>
</front>
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<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
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<name sortKey="Geng, Qianqian" sort="Geng, Qianqian" uniqKey="Geng Q" first="Qianqian" last="Geng">Qianqian Geng</name>
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<country name="États-Unis"><noRegion><name sortKey="Guo, Chunfang" sort="Guo, Chunfang" uniqKey="Guo C" first="Chunfang" last="Guo">Chunfang Guo</name>
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<name sortKey="Kresty, Laura A" sort="Kresty, Laura A" uniqKey="Kresty L" first="Laura A" last="Kresty">Laura A. Kresty</name>
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Circular RNA circHIPK3 modulates autophagy via MIR124-3p-STAT3-PRKAA/AMPKα signaling in STK11 mutant lung cancer.

Circular RNA circHIPK3 modulates autophagy via MIR124-3p-STAT3-PRKAA/AMPKα signaling in STK11 mutant lung cancer.

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Abstract

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