MicroRNA-7 inhibits proliferation, migration and invasion of thyroid papillary cancer-cells via targeting CKS2

被引：57

作者：

Hua, Kaiyao ^{[1
,2
]}

Jin, Jiali ^{[3
]}

Zhang, Huiwen ^{[2
]}

Zhao, Bingkun ^{[1
,2
]}

Wu, Chenyang ^{[1
]}

Xu, Hui ^{[1
]}

Fang, Lin ^{[1
]}

机构：

[1] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Breast & Thyroid Surg, 301 Yanchang Rd, Shanghai 200072, Peoples R China

[2] Nanjing Med Univ, Nanjing 210029, Jiangsu, Peoples R China

[3] Tongji Univ, Sch Med, Shanghai 200072, Peoples R China

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2016年 / 49卷 / 04期

基金：

中国国家自然科学基金;

关键词：

miR-7; proliferation; CKS2; thyroid papillary cancer; GROWTH-FACTOR RECEPTOR; KINASE SUBUNIT-2; TUMOR-SUPPRESSOR; EXPRESSION; MIR-7;

D O I：

10.3892/ijo.2016.3660

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The purpose of this study was to examine the expression levels of microRNA-7 (miR-7) in human thyroid papillary cancer and its potential role in disease pathogenesis. The expression levels of different miRNAs were detected by miRNA-microarray analysis in ten thyroid papillary cancer specimens and adjacent normal thyroid cancer tissues. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to determine the expression level of miR-7 in both thyroid papillary cancer tissues and cell lines. To characterize the function of miR-7, MTT assay, colony formation assay, cell migration assay, cell invasion assay, cell cycle assay and cell apoptosis assay were used. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-7, in corroboration with western blot assays. Finally, MTT assay, cell migration assay, cell invasion assay and cell cycle assay were used to indicate the roles of endogenous cyclin-dependent kinase regulatory subunit 2 (CKS2) in thyroid papillary cancer cells. Our results reveal that miR-7 expression was relatively decreased in thyroid papillary cancer specimens and cell lines compared with adjacent normal tissues and normal thyroid cells. Overexpression of miR-7 inhibited cellular proliferation, suppressed cellular migration and invasion, caused a G0/G1 arrest in vitro. Dual-luciferase reporter assays showed that miR-7 binds the 3'-untranslated region (3'-UTR) of CKS2. Western blotting showed that miR-7 negatively regulated CKS2 protein expression. As its downstream genes, cyclin B1 (G2/mitotic-specific cyclin-B1) and cdk1 (cyclin-dependent kinase 1) were regulated by miR-7 and CKS2 axis. Knockdown of CKS2 expression by CKS2-siRNA in TPC1 and K1 cells also significantly suppressed cell proliferation, cell migration and invasion. Our results demonstrated for the first time that miR-7 functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting CKS2 in thyroid papillary cancer cells.

引用

页码：1531 / 1540

页数：10

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