Screening and molecular mechanism research on bile microRNAs associated with chemotherapy efficacy in perihilar cholangiocarcinoma.

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-12-04 eCollection Date: 2024-12-20 DOI:10.1016/j.isci.2024.111437

Shijie Fu, Haizhen Du, Yuyang Dai, Kanglian Zheng, Guang Cao, Liang Xu, Yujie Zhong, Chuanxin Niu, Yan Kong, Xiaodong Wang

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引用次数: 0

Abstract

The efficacy of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin (OXA) and 5-fluorouracil (5-Fu) for treating advanced perihilar cholangiocarcinoma (pCCA) has been demonstrated, yet the survival benefits of HAIC for pCCA patients vary. Here, we aimed to screen out HAIC resistance-related bile microRNAs (miRNAs) and explore the functions of specific bile miRNAs in pCCA based on high-throughput sequencing. Levels of bile miR-532-3p, miR-1250-5p, and miR-4772-5p were related to the survival of advanced pCCA patients after HAIC. However, only overexpression of miR-532-3p promoted OXA/5-Fu resistance, and downregulation of its expression improved sensitivity to OXA/5-Fu. Mechanistic investigations revealed secreted protein acidic and rich in cysteine (SPARC) as the direct target of miR-532-3p. Our study reveals that bile miR-532-3p, miR-1250-5p, and miR-4772-5p may serve as survival biomarkers in advanced pCCA patients after HAIC and that bile miR-532-3p promotes resistance to HAIC with OXA and 5-Fu via negatively regulating SPARC expression.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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