ARID1A promotes chemosensitivity to gemcitabine in pancreatic cancer through epigenetic silencing of RRM2.

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL Pharmazie Pub Date : 2022-09-01 DOI:10.1691/ph.2022.1881

Wenyi Li, Qiwei Chen, Weiwei Gao, Hui Zeng

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引用次数: 1

Abstract

Pancreatic cancer is one of the most common malignancies with very poor prognosis due to its broad resistance to chemotherapy. ARID1A, a subunit of SWI/SNF complex, is involved in pancreatic carcinogenesis through epigenetic silencing of oncogenes. In this study, we aimed to explore whether ARID1A was implicated in the gemcitabine resistance in pancreatic cancer patients via regulating RRM2. We examined the effect of ARID1A depletion on the gemcitabine sensitivity in pancreatic cancer cells and explored the role of RRM2 in ARID1A-mediated pancreatic cancer cells chemosensitivity to gemcitabine. We found that Knockout of ARID1A led to gemcitabine resistance in pancreatic cancer cells, effect of which could be reversed by RRM2, a gemcitabine resistance related gene. ARID1A decreased the transcription of RRM2, and directly bound to the promoter of RRM2. Moreover, expression of RRM2 was negatively correlated with ARID1A in pancreatic cancer tissues. Thus, ARID1A-mediated RRM2 epigenetic suppression is crucial for enhancement of pancreatic cancer chemosensitivity to gemcitabine, and ARID1A could be used as a biomarker to guide the gemcitabine chemotherapy of pancreatic cancer.

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ARID1A 通过表观遗传沉默 RRM2 促进胰腺癌患者对吉西他滨的化疗敏感性。

胰腺癌是最常见的恶性肿瘤之一，由于其对化疗的广泛耐药性，预后极差。ARID1A是SWI/SNF复合物的一个亚基，通过表观遗传沉默癌基因参与胰腺癌的发生。本研究旨在探讨 ARID1A 是否通过调节 RRM2 与胰腺癌患者的吉西他滨耐药性有关。我们研究了 ARID1A 缺失对胰腺癌细胞吉西他滨敏感性的影响，并探讨了 RRM2 在 ARID1A 介导的胰腺癌细胞对吉西他滨化学敏感性中的作用。我们发现，敲除 ARID1A 会导致胰腺癌细胞对吉西他滨产生耐药性，而吉西他滨耐药性相关基因 RRM2 可以逆转这种耐药性。ARID1A 可降低 RRM2 的转录，并直接与 RRM2 的启动子结合。此外，在胰腺癌组织中，RRM2的表达与ARID1A呈负相关。因此，ARID1A介导的RRM2表观遗传抑制是增强胰腺癌对吉西他滨化疗敏感性的关键，ARID1A可作为生物标志物指导胰腺癌的吉西他滨化疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmazie 医学-化学综合

CiteScore

3.10

自引率

0.00%

发文量

审稿时长

1.2 months

期刊介绍： The journal DiePharmazie publishs reviews, experimental studies, letters to the editor, as well as book reviews. The following fields of pharmacy are covered: Pharmaceutical and medicinal chemistry; Pharmaceutical analysis and drug control; Pharmaceutical technolgy; Biopharmacy (biopharmaceutics, pharmacokinetics, biotransformation); Experimental and clinical pharmacology; Pharmaceutical biology (pharmacognosy); Clinical pharmacy; History of pharmacy.