title: miR-490-3p inhibits the growth and invasiveness in triple-negative breast cancer by repressing the expression of TNKS2.
abstract: Identification of key genes driving the aggressiveness of triple-negative breast cancer (TNBC) is important to develop effective therapies. In this study, we examined the expression and biological roles of microRNA (miR)-490-3p in TNBC. Our data showed that miR-490-3p-3p was underexpressed in TNBC compared with non-TNBC tissues (P=0.0021). Similarly, this miRNA was expressed at lower levels in TNBC cell lines than in non-TNBC cell lines. Gain-of-function studies revealed that miR-490-3p-3p overexpression inhibited cell growth and invasion in both MDA-MB-231 and MDA-MB-436 TNBC cells and impaired tumorigenesis of MDA-MB-231 cells in nude mice. Mechanistically, we found that miR-490-3p negatively regulated the expression of tankyrase 2 (TNKS2) via binding to its 3'-untranslated region and then blocked the activation of β-catenin signaling. Importantly, overexpression of a miR-490-3p-resistant form of TNKS2 reversed miR-490-3p-mediated suppression of TNBC cell proliferation and invasion. Knockdown of TNKS2 via small interfering RNA technology was found to mimic the suppressive activity of miR-490-3p in MDA-MB-231 cells. Taken together, miR-490-3p is downregulated in TNBC and plays a suppressive role in cancer cell proliferation, invasion, and tumorigenesis. The tumor suppressive activity of miR-490-3p is largely mediated through downregulation of TNKS2 and inactivation of β-catenin signaling. Thus, miR-490-3p may represent a potential therapeutic target for TNBC.
authors: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, China. Electronic address: zj_2016am@163.com.
authors: Zhongming
authors: Z
authors: Jia
authors: Department of Gynecology, Binzhou People's Hospital, Binzhou, China.
authors: Yan
authors: Y
authors: Liu
authors: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, China.
authors: Qiang
authors: Q
authors: Gao
authors: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, China.
authors: Yong
authors: Y
authors: Han
authors: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, China.
authors: Guoqiang
authors: G
authors: Zhang
authors: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, China.
authors: Shujian
authors: S
authors: Xu
authors: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, China.
authors: Kai
authors: K
authors: Cheng
authors: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, China.
authors: Weiwei
authors: W
authors: Zou
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009368:Neoplasm Transplantation; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D038501:Tankyrases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C574862:MIRN490 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C437334:TNKS2 protein, human; D038501:Tankyrases
keywords: Breast cancer; Growth; Metastasis; TNKS2; microRNA