miR-663a inhibits hepatocellular carcinoma cell proliferation and invasion by targeting HMGA2

被引:45
作者
Huang, Weizhen [1 ]
Li, Jun [1 ]
Guo, Xiaohong [1 ]
Zhao, Yingchu [2 ]
Yuan, Xia [1 ]
机构
[1] Huizhou Municipal Cent Hosp Guangdong Prov, Dept Med Oncol, 41 North Eling Rd, Huizhou 516000, Guangdong, Peoples R China
[2] Univ Missouri, Dept Biochem, 117 Schweitzer Hall, Columbia, MO 65211 USA
关键词
Hepatocellular carcinoma; miR-663a; HMGA2; NONCODING RNA; MESENCHYMAL TRANSITION; BETA-CATENIN; TUMOR-GROWTH; PROMOTES; METASTASIS; EXPRESSION; OVEREXPRESSION; BIOMARKERS; MICRORNAS;
D O I
10.1016/j.biopha.2016.04.034
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
Hepatocellular carcinoma (HCC) is a highly aggressive solid malignancy throughout the world. Dysregulation of miRNAs play essential roles in HCC progression via aberrant regulation of cell proliferation, apoptosis, as well as metastasis. miR-663a is a poorly investigated miRNA. Whether miR-663a regulates HCC development remains unknown. The aim of the study was to explore the role of miR-663a in HCC development. To determine the expression level of miR-663a in HCC, we analyzed the data from GSE21362 and TCGA. The results showed that miR-663a was significantly down-regulated in HCC tissue compared with adjacent non-tumor tissue. Gain of function and loss of function assays revealed that miR-663a distinctly inhibited cell proliferation, migration and invasion. Mechanistic investigations demonstrated that miR-663a modulated cell functions through targeting and suppressing high mobility group A2 (HMGA2). In addition, overexpression of HMGA2 remarkably attenuated the tumor repressive effect of miR-663a. Taken together, miR-663a inhibits HCC cell proliferation and motility by targeting HMGA2. (C) 2016 Published by Elsevier Masson SAS.
引用
收藏
页码:431 / 438
页数:8
相关论文
共 40 条
[1]   The Long Intergenic Noncoding RNA UFC1, a Target of MicroRNA 34a, Interacts With the mRNA Stabilizing Protein HuR to Increase Levels of β-Catenin in HCC Cells [J].
Cao, Chuanhui ;
Sun, Jingyuan ;
Zhang, Dongyan ;
Guo, Xuejun ;
Xie, Liwei ;
Li, Xin ;
Wu, Dehua ;
Liu, Li .
GASTROENTEROLOGY, 2015, 148 (02) :415-U249
[2]   MicroRNA-331-3p Promotes Proliferation and Metastasis of Hepatocellular Carcinoma by Targeting PH Domain and Leucine-Rich Repeat Protein Phosphatase [J].
Chang, Rui-Min ;
Yang, Hao ;
Fang, Feng ;
Xu, Jiang-Feng ;
Yang, Lian-Yue .
HEPATOLOGY, 2014, 60 (04) :1251-1263
[3]   Differential expression of cellular microRNAs in HPV-11 transfected cells. An analysis by three different array platforms and qRT-PCR [J].
Dreher, Anita ;
Rossing, Maria ;
Kaczkowski, Bogumil ;
Nielsen, Finn Cilius ;
Norrild, Bodil .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 403 (3-4) :357-362
[4]   MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma [J].
Fang, Feng ;
Chang, Rui-min ;
Yu, Lei ;
Lei, Xiong ;
Xiao, Shuai ;
Yang, Hao ;
Yang, Lian-Yue .
JOURNAL OF HEPATOLOGY, 2015, 63 (04) :874-885
[5]   HMGA2: A pituitary tumour subtype-specific oncogene? [J].
Fedele, Monica ;
Palmieri, Dario ;
Fusco, Alfredo .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2010, 326 (1-2) :19-24
[6]   Hallmarks of Cancer: The Next Generation [J].
Hanahan, Douglas ;
Weinberg, Robert A. .
CELL, 2011, 144 (05) :646-674
[7]   The Overexpression of Hypomethylated miR-663 Induces Chemotherapy Resistance in Human Breast Cancer Cells by Targeting Heparin Sulfate Proteoglycan 2 (HSPG2) [J].
Hu, Haiyan ;
Li, Shuqin ;
Cui, Xiuying ;
Lv, Xiaobin ;
Jiao, Yu ;
Yu, Fengyan ;
Yao, Herui ;
Song, Erwei ;
Chen, Yongsong ;
Wang, Minghui ;
Lin, Ling .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (16) :10973-10985
[8]   Downregulation of adenomatous polyposis coli by microRNA-663 promotes odontogenic differentiation through activation of Wnt/beta-catenin signaling [J].
Kim, Jae-Sung ;
Park, Min-Gyeong ;
Lee, Seul Ah ;
Park, Sun-Young ;
Kim, Heung-Joong ;
Yu, Sun-Kyoung ;
Kim, Chun Sung ;
Kim, Su-Gwan ;
Oh, Ji-Su ;
You, Jae-Seek ;
Kim, Jin-Soo ;
Seo, Yo-Seob ;
Chun, Hong Sung ;
Park, Joo-Cheol ;
Kim, Do Kyung .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2014, 446 (04) :894-900
[9]   MicroRNAs as Potential Biomarkers in Cancer: Opportunities and Challenges [J].
Lan, Huiyin ;
Lu, Haiqi ;
Wang, Xian ;
Jin, Hongchuan .
BIOMED RESEARCH INTERNATIONAL, 2015, 2015
[10]   HMGA2 induces transcription factor Slug expression to promote epithelial-to-mesenchymal transition and contributes to colon cancer progression [J].
Li, Yang ;
Zhao, Zhongxin ;
Xu, Chuanhui ;
Zhou, Zhuqing ;
Zhu, Zhe ;
You, Tiangeng .
CANCER LETTERS, 2014, 355 (01) :130-140