Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer

被引：230

作者：

Wang, J. ^{[1
]}

Tian, X. ^{[1
]}

Han, R. ^{[1
]}

Zhang, X. ^{[2
]}

Wang, X. ^{[3
]}

Shen, H. ^{[1
]}

Xue, L. ^{[1
]}

Liu, Y. ^{[3
]}

Yan, X. ^{[1
]}

Shen, J. ^{[4
]}

Mannoor, K. ^{[4
]}

Deepak, J. ^{[5
]}

Donahue, J. M. ^{[6
]}

Stass, S. A. ^{[4
]}

Xing, L. ^{[1
]}

Jiang, F. ^{[4
]}

机构：

[1] Hebei Med Univ, Dept Pathol, Shijiazhuang 050017, Peoples R China

[2] Hebei Med Univ, Hosp 2, Dept Pathol, Shijiazhuang 050017, Peoples R China

[3] Hebei Med Univ, Tumor Hosp, Dept Pathol, Shijiazhuang 050017, Peoples R China

[4] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA

[5] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA

[6] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA

来源：

ONCOGENE | 2014年 / 33卷 / 09期

基金：

中国国家自然科学基金;

关键词：

miR-486-5p; tumor-suppressor gene; lung cancer; ARHGAP5; therapy; MICRORNA MARKERS; P190B RHOGAP; CELL; SUPPRESSOR; CARCINOMA; IDENTIFICATION; TUMORIGENESIS; ACTIVATION; BIOMARKERS; DIAGNOSIS;

D O I：

10.1038/onc.2013.42

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

We have previously shown that miR-486-5p is one of the most downregulated micro RNAs in lung cancer. The objective of the study was to investigate the role of miR-486-5p in the progression and metastasis of non-small-cell lung cancer (NSCLC). We evaluated miR-486-5p expression status on 76 frozen and 33 formalin-fixed paraffin-embedded tissues of NSCLC by quantitative reverse transcriptase PCR to determine its clinicopathologic significance. We then performed function analysis of miR-486-5p to determine its potential roles on cancer cell migration and invasion in vitro and metastasis in vivo. We also investigated the target genes of miR-486-5p in lung tumorigenesis. miR-486-5p expression level was significantly lower in lung tumors compared with their corresponding normal tissues (P<0.0001), and associated with stage (P = 0.0001) and lymph node metastasis of NSCLC (P = 0.0019). Forced expression of miR-486-5p inhibited NSCLC cell migration and invasion in vitro and metastasis in mice by inhibiting cell proliferation. Furthermore, ectopic expression of miR-486-5p in cancer cells reduced ARHGAP5 expression level, whereas miR-486-5p silencing increased its expression. Luciferase assay demonstrated that miR-486-5p could directly bind to the 30-untranslated region of ARHGAP5. The expression level of miR-486-5p was inversely correlated with that of ARHGAP5 in lung tumor tissues (P = 0.0156). Reduced expression of ARHGAP5 considerably inhibited lung cancer cell migration and invasion, resembling that of miR-486-5p overexpression. miR-486-5p may act as a tumor-suppressor contributing to the progression and metastasis of NSCLC by targeting ARHGAP5. miR-486-5p would provide potential diagnostic and therapeutic targets for the disease.

引用

页码：1181 / 1189

页数：9

共 32 条

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