title: MicroRNA-34a-5p enhances sensitivity to chemotherapy by targeting AXL in hepatocellular carcinoma MHCC-97L cells.
abstract: Mature microRNA (miRNA) 34a-5p, which is a well-known tumor suppressor in hepatitis virus-associated hepatocellular carcinoma (HCC), plays an important role in cell processes, such as cell proliferation and apoptosis, and is therefore an optimal biomarker for future clinical use. However, the role of miRNA-34a-5p in chemoresistance has yet to be identified. In the present study, the expression of miRNA-34a-5p was assessed by anin situhybridization assay in HCC tissues and was found to be significantly decreased compared with the pericarcinomatous areas of the tissue specimens, which consisted of samples obtained from 114 patients with HCC. High expression of miRNA-34a-5p was found to be associated with a favorable overall survival time in HCC patients. Functional tests performed by transfecting miRNA-34a-5p mimics or inhibitors into MHCC-97L cells illustrated that miRNA-34a-5p inhibited proliferation, elevated apoptosis and decreased chemoresistance to cisplatin in HCC cells. AXL is the direct target of miRNA-34a-5p, as confirmed by sequence analysis and luciferase assay. Transfection of the cells with small interfering RNA for AXL (siAXL) increased the apoptosis ratio of the MHCC-97L cell line. Transfection with siAXL led to similar biological behaviors in the MHCC-97L cells to those induced by ectopic expression of miRNA-34a-5p. Thus, it was concluded that miRNA-34a-5p enhanced the sensitivity of the cells to chemotherapy by targeting AXL in hepatocellular carcinoma. In addition, low expression of miRNA-34a-5p in HCC tissues yielded an unfavorable prognosis for patients with HCC that received radical surgery, due to the promotion of proliferation and an increase in chemoresistance in HCC cells.
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Jing-Yun
authors.initials: JY
authors.lastname: Wen
authors.affiliation: Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Chang-Chang
authors.initials: CC
authors.lastname: Jia
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Q U
authors.initials: QU
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Zhan-Hong
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Ma
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Wei
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Ze-Xiao
authors.initials: ZX
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Dan-Yun
authors.initials: DY
authors.lastname: Ruan
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Dong-Hao
authors.initials: DH
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tai
authors.affiliation: Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Xiong
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, Gunagdong 510630, P.R. China.
authors.forename: Q I
authors.initials: QI
authors.lastname: Zhang
keywords: AXL; chemoresistance; cisplatin; hepatocellular carcinoma; microRNA34a-5p