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顺铂耐药卵巢癌中COL1A1的详细分子机制及潜在药物

Detailed Molecular Mechanism and Potential Drugs for COL1A1 in Carboplatin-Resistant Ovarian Cancer.

作者信息

Yang Feng, Zhao Ziyu, Cai Shaoyi, Ling Li, Hong Leying, Tao Liang, Wang Qin

机构信息

Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.

School of Pharmacy, Sun Yat-Sen University, Guangzhou, China.

出版信息

Front Oncol. 2021 Feb 17;10:576565. doi: 10.3389/fonc.2020.576565. eCollection 2020.

DOI:10.3389/fonc.2020.576565
PMID:33680916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7928381/
Abstract

Carboplatin resistance in ovarian cancer (OV) is a major medical problem. Thus, there is an urgent need to find novel therapeutic targets to improve the prognosis of patients with carboplatin-resistant OV. Accumulating evidence indicates that the gene COL1A1 (collagen type I alpha 1 chain) has an important role in chemoresistance and could be a therapeutic target. However, there have been no reports about the role of COL1A1 in carboplatin-resistant OV. This study aimed to establish the detailed molecular mechanism of COL1A1 and predict potential drugs for its treatment. We found that COL1A1 had a pivotal role in carboplatin resistance in OV by weighted gene correlation network analysis and survival analysis. Moreover, we constructed a competing endogenous RNA network (LINC00052/SMCR5-miR-98-COL1A1) based on multi-omics data and experiments to explore the upstream regulatory mechanisms of COL1A1. Two key pathways involving COL1A1 in carboplatin resistance were identified by co-expression analysis and pathway enrichment: the "ECM-receptor interaction" and "focal adhesion" Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, combining these results with those of cell viability assays, we proposed that ZINC000085537017 and quercetin were potential drugs for COL1A1 based on virtual screening and the TCMSP database, respectively. These results might help to improve the outcome of OV in the future.

摘要

卵巢癌（OV）中的卡铂耐药是一个重大医学问题。因此，迫切需要找到新的治疗靶点以改善卡铂耐药性OV患者的预后。越来越多的证据表明，基因COL1A1（I型胶原蛋白α1链）在化疗耐药中起重要作用，可能是一个治疗靶点。然而，关于COL1A1在卡铂耐药性OV中的作用尚无报道。本研究旨在确定COL1A1的详细分子机制，并预测其治疗的潜在药物。通过加权基因共表达网络分析和生存分析，我们发现COL1A1在OV的卡铂耐药中起关键作用。此外，我们基于多组学数据和实验构建了一个竞争性内源性RNA网络（LINC00052/SMCR5-miR-98-COL1A1），以探索COL1A1的上游调控机制。通过共表达分析和通路富集确定了COL1A1在卡铂耐药中的两条关键通路：京都基因与基因组百科全书（KEGG）通路中的“细胞外基质受体相互作用”和“粘着斑”通路。此外，将这些结果与细胞活力测定结果相结合，我们分别基于虚拟筛选和中药系统药理学数据库（TCMSP）提出ZINC000085537017和槲皮素是COL1A1的潜在药物。这些结果可能有助于未来改善OV的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/141683d4fa58/fonc-10-576565-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/5f80176169e9/fonc-10-576565-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/09244ee3cb27/fonc-10-576565-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/a9c3563de42f/fonc-10-576565-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/37ba66bbd253/fonc-10-576565-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/e1480cd30f7a/fonc-10-576565-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/141683d4fa58/fonc-10-576565-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/5f80176169e9/fonc-10-576565-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/09244ee3cb27/fonc-10-576565-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/a9c3563de42f/fonc-10-576565-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5396/7928381/141683d4fa58/fonc-10-576565-g006.jpg

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