miRNA-10a-5p inhibits cell metastasis in hepatocellular carcinoma via targeting SKA1

被引:17
作者
Shen, Duo [1 ]
Zhao, Hong-Yu [2 ]
Gu, Ai-Dong [3 ]
Wu, Yin-Wei [2 ]
Weng, Yu-Hang [4 ]
Li, Shu-Jie [3 ]
Song, Jin-Yun [2 ]
Gu, Xue-Feng [1 ]
Qiu, Jie [1 ,4 ]
Zhao, Wei [1 ,4 ]
机构
[1] Southeast Univ, Med Sch, 87 Dingjiaqiao Rd, Nanjing 210000, Peoples R China
[2] Nanjing Univ Chinese Med, Hosp Nanjing 2, Dept Clin Res Ctr, Nanjing, Peoples R China
[3] Nanjing Univ Chinese Med, Hosp Nanjing 2, Dept Hepatobiliary & Pancreat Surg, Nanjing, Peoples R China
[4] Nanjing Univ Chinese Med, Hosp Nanjing 2, Dept Hepatol, Nanjing, Peoples R China
关键词
epithelial– mesenchymal transition; hepatocellular carcinoma; miR‐ 10a‐ 5p; SKA1; CANCER; SPINDLE;
D O I
10.1002/kjm2.12392
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
A variety of microRNAs (miRNAs) are involved in the occurrence and development of hepatocellular carcinoma (HCC). However, the role of miR-10a-5p in the progression of HCC remains unclear. Therefore, the purpose of this study was to determine the role of miR-10a-5p in the development of HCC and the possible molecular mechanism. miR-10a-5p expression in HCC tissues and plasma from patients was detected by quantitative real-time polymerase chain reaction. Migratory changes in HCC cells were detected after the overexpression of miR-10a-5p. Epithelial-mesenchymal transition (EMT)-related proteins were detected by Western blot. Finally, through luciferase assay and rescue experiments, the mechanism by which miR-10a-5p regulates its downstream gene, human spindle and kinetochore-associated complex subunit 1, SKA1 and the interaction between these molecules in the development of HCC were determined. The expression of miR-10a-5p was markedly downregulated in HCC tissues, cell lines, and plasma. The overexpression of miR-10a-5p significantly inhibited the migration, invasion, and EMT of HCC cells. Furthermore, SKA1 was shown to be a downstream gene of miR-10a-5p. SKA1 silencing had the same effect as miR-10a-5p overexpression in HCC. In particular, the overexpression of SKA1 reversed the inhibitory effects of miR-10a-5p in HCC. Taken together, low miR-10a-5p expression is associated with HCC progression. miR-10a-5p inhibits the malignant development of HCC by negatively regulating SKA1.
引用
收藏
页码:784 / 794
页数:11
相关论文
共 27 条
[1]   Structural basis for microtubule recognition by the human kinetochore Ska complex [J].
Abad, Maria Alba ;
Medina, Bethan ;
Santamaria, Anna ;
Zou, Juan ;
Plasberg-Hill, Carla ;
Madhumalar, Arumugam ;
Jayachandran, Uma ;
Redli, Patrick Marc ;
Rappsilber, Juri ;
Nigg, Erich A. ;
Jeyaprakash, A. Arockia .
NATURE COMMUNICATIONS, 2014, 5
[2]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   Hepatocellular carcinoma: clinical frontiers and perspectives [J].
Bruix, Jordi ;
Gores, Gregory J. ;
Mazzaferro, Vincenzo .
GUT, 2014, 63 (05) :844-855
[5]   SKA1/2/3 serves as a biomarker for poor prognosis in human lung adenocarcinoma [J].
Chen, Cheng ;
Guo, Qiang ;
Song, Yongxiang ;
Xu, Gang ;
Liu, Lunxu .
TRANSLATIONAL LUNG CANCER RESEARCH, 2020, 9 (02) :218-+
[6]   SKA1 overexpression is associated with poor prognosis in hepatocellular carcinoma [J].
Chen, Yibing ;
Zhao, Jingjing ;
Jiao, Zhihui ;
Wang, Weiwei ;
Wang, Dandan ;
Yu, Xiaohe ;
Shi, Zhiyong ;
Ge, Naijian ;
Pan, Qiuzhong ;
Xia, Jianchuan ;
Niu, Wancheng ;
Zhao, Ruihua ;
Zhang, Xiaofei ;
Du, Wei .
BMC CANCER, 2018, 18
[7]   Long non-coding RNA ZFAS1 promotes proliferation and metastasis of clear cell renal cell carcinoma via targeting miR-10a/SKA1 pathway [J].
Dong, Dan ;
Mu, Zhongyi ;
Wei, Ning ;
Sun, Mingli ;
Wang, Wei ;
Xin, Na ;
Shao, Yue ;
Zhao, Chenghai .
BIOMEDICINE & PHARMACOTHERAPY, 2019, 111 :917-925
[8]   Regulation of mRNA Translation and Stability by microRNAs [J].
Fabian, Marc Robert ;
Sonenberg, Nahum ;
Filipowicz, Witold .
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 79, 2010, 79 :351-379
[9]   miRNAs in human cancer [J].
Farazi, Thalia A. ;
Spitzer, Jessica I. ;
Morozov, Pavel ;
Tuschl, Thomas .
JOURNAL OF PATHOLOGY, 2011, 223 (02) :102-115
[10]   The Down-Regulation of TrkB Alleviates the Malignant Biological Behavior and Cancer Stem-Like Property of Laryngeal Cancer [J].
Hu, Xiaoyan ;
Zou, Wujun ;
Liu, Dianzhong ;
Qin, Gang ;
Jiang, Liang .
CANCER MANAGEMENT AND RESEARCH, 2020, 12 :6865-6875