Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer
Identifieur interne : 000087 ( an2020/Analysis ); précédent : 000086; suivant : 000088Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer
Auteurs : Xin-Yue Gu [République populaire de Chine] ; Yang Jiang [République populaire de Chine] ; Ming-Qi Li [République populaire de Chine] ; Peng Han [République populaire de Chine] ; Yan-Long Liu [République populaire de Chine] ; Bin-Bin Cui [République populaire de Chine]Source :
- Aging (Albany NY) [ 1945-4589 ] ; 2020.
Abstract
A promising new strategy for cancer therapy is to target the autophagic pathway. However, comprehensive characterization of autophagy genes and their clinical relevance in cancer is still lacking. Here, we systematically characterized alterations of autophagy genes in multiple cancer lines by analyzing data from The Cancer Genome Atlas and CellMiner database. Interactions between autophagy genes and clinically actionable genes (CAGs) were identified by analyzing co-expression, protein-protein interactions (PPIs) and transcription factor (TF) data. A key subnetwork was identified that included 18 autophagy genes and 22 CAGs linked by 28 PPI pairs and 1 TF-target pair, which was EGFR targeted by RARA. Alterations in the expression of autophagy genes were associated with patient survival in multiple cancer types. RARA and EGFR were associated with worse survival in colorectal cancer patients. The regulatory role of EGFR in 5-FU resistance was validated in colon cancer cells in vivo and in vitro. EGFR contributed to 5-FU resistance in colon cancer cells through autophagy induction, and EGFR overexpression in 5-FU resistant colon cancer was regulated by RARA. The present study provides a comprehensive analysis of autophagy in different cancer cell lines and highlights the potential clinical utility of targeting autophagy genes.
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DOI: 10.18632/aging.102607
PubMed: 31896739
PubMed Central: 6977699
Affiliations:
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PMC:6977699Le document en format XML
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150040</wicri:noRegion></affiliation></author></analytic><series><title level="j">Aging (Albany NY)</title><idno type="eISSN">1945-4589</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A promising new strategy for cancer therapy is to target the autophagic pathway. 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EGFR contributed to 5-FU resistance in colon cancer cells through autophagy induction, and EGFR overexpression in 5-FU resistant colon cancer was regulated by RARA. 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