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

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

  • iScience. 2024 Dec 4;27(12):111437. doi: 10.1016/j.isci.2024.111437.
Shijie Fu 1,  Haizhen Du 2,  Yuyang Dai 3,  Kanglian Zheng 3,  Guang Cao 3,  Liang Xu 3,  Yujie Zhong 3,  Chuanxin Niu 3,  Yan Kong 2,  Xiaodong Wang 3
Affiliations

Affiliations

  • 1 Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100000, China.
  • 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing 100142, China.
  • 3 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
PMID: 39717085 DOI: 10.1016/j.isci.2024.111437
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.

Keywords

Cancer; Cell biology; Molecular biology.

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