Screening and molecular mechanism research on bile microRNAs associated with chemotherapy efficacy in perihilar cholangiocarcinoma
Shijie Fu,
Haizhen Du,
Yuyang Dai,
Kanglian Zheng,
Guang Cao,
Liang Xu,
Yujie Zhong,
Chuanxin Niu,
Yan Kong,
Xiaodong Wang
Affiliations
Shijie Fu
Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100000, China
Haizhen Du
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
Yuyang Dai
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Kanglian Zheng
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Guang Cao
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Liang Xu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Yujie Zhong
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Chuanxin Niu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Yan Kong
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; Corresponding author
Xiaodong Wang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China; Corresponding author
Summary: 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.
