PTBP3 promotes malignancy and hypoxia‐induced chemoresistance in pancreatic cancer cells by ATG12 up‐regulation
Identifieur interne : 000E72 ( Ncbi/Checkpoint ); précédent : 000E71; suivant : 000E73PTBP3 promotes malignancy and hypoxia‐induced chemoresistance in pancreatic cancer cells by ATG12 up‐regulation
Auteurs : Jun Ma ; Li Weng ; Yiping Jia ; Bingyan Liu ; Shaoqiu Wu ; Lei Xue ; Xiang Yin ; Aiwu Mao ; Zhongmin Wang ; Mingyi ShangSource :
- Journal of Cellular and Molecular Medicine [ 1582-1838 ] ; 2020.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) tumours exhibit a high level of heterogeneity which is associated with hypoxia and strong resistance to chemotherapy. The RNA splicing protein polypyrimidine tract‐binding protein 3 (PTBP3) regulates hypoxic gene expression by selectively binding to hypoxia‐regulated transcripts. We have investigated the role of PTBP3 in tumour development and chemotherapeutic resistance in human PDAC tissues and pancreatic cancer cells. In addition, we determined the sensitivity of cancer cells to gemcitabine with differential levels of PTBP3 and whether autophagy and hypoxia affect gemcitabine resistance in vitro. PTBP3 expression was higher in human pancreatic cancer than in paired adjacent tissues. PTBP3 overexpression promoted PDAC proliferation in vitro and tumour growth in vivo
Url:
DOI: 10.1111/jcmm.14896
PubMed: 31989778
PubMed Central: 7077536
Affiliations:
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>Pancreatic ductal adenocarcinoma (PDAC) tumours exhibit a high level of heterogeneity which is associated with hypoxia and strong resistance to chemotherapy. The RNA splicing protein polypyrimidine tract‐binding protein 3 (PTBP3) regulates hypoxic gene expression by selectively binding to hypoxia‐regulated transcripts. We have investigated the role of PTBP3 in tumour development and chemotherapeutic resistance in human PDAC tissues and pancreatic cancer cells. In addition, we determined the sensitivity of cancer cells to gemcitabine with differential levels of PTBP3 and whether autophagy and hypoxia affect gemcitabine resistance in vitro. PTBP3 expression was higher in human pancreatic cancer than in paired adjacent tissues. PTBP3 overexpression promoted PDAC proliferation in vitro and tumour growth in vivo<italic>,</italic>
whereas PTBP3 depletion had opposing effects. Hypoxia significantly increased the expression of PTBP3 in pancreatic cancer cells in vitro. Under hypoxic conditions, cells were more resistance to gemcitabine. Knockdown of PTBP3 results in decreased resistance to gemcitabine, which was attributed to attenuated autophagy. We propose that PTBP3 binds to multiple sites in the 3′‐UTR of ATG12 resulting in overexpression. PTBP3 increases cancer cell proliferation and autophagic flux in response to hypoxic stress, which contributes to gemcitabine resistance.</p>
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<name sortKey="Liu, Bingyan" sort="Liu, Bingyan" uniqKey="Liu B" first="Bingyan" last="Liu">Bingyan Liu</name>
<name sortKey="Ma, Jun" sort="Ma, Jun" uniqKey="Ma J" first="Jun" last="Ma">Jun Ma</name>
<name sortKey="Mao, Aiwu" sort="Mao, Aiwu" uniqKey="Mao A" first="Aiwu" last="Mao">Aiwu Mao</name>
<name sortKey="Shang, Mingyi" sort="Shang, Mingyi" uniqKey="Shang M" first="Mingyi" last="Shang">Mingyi Shang</name>
<name sortKey="Wang, Zhongmin" sort="Wang, Zhongmin" uniqKey="Wang Z" first="Zhongmin" last="Wang">Zhongmin Wang</name>
<name sortKey="Weng, Li" sort="Weng, Li" uniqKey="Weng L" first="Li" last="Weng">Li Weng</name>
<name sortKey="Wu, Shaoqiu" sort="Wu, Shaoqiu" uniqKey="Wu S" first="Shaoqiu" last="Wu">Shaoqiu Wu</name>
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