miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma

被引：99

作者：

Dong, Ruifen ^{[1
]}

Liu, Xiaolin ^{[1
]}

Zhang, Qing ^{[1
]}

Jiang, Zhijun ^{[1
]}

Li, Yingwei ^{[1
]}

Wei, Yuyan ^{[1
]}

Li, Yinuo ^{[1
]}

Yang, Qifeng ^{[5
]}

Liu, Jinsong ^{[7
]}

Wei, Jian-Jun ^{[6
]}

Shao, Changshun ^{[3
,4
]}

Liu, Zhaojian ^{[2
]}

Kong, Beihua ^{[1
]}

机构：

[1] Shandong Univ, Dept Obstet & Gynecol, Qilu Hosp, Jinan 250100, Shandong, Peoples R China

[2] Shandong Univ, Dept Cell Biol, Sch Med, Jinan 250100, Shandong, Peoples R China

[3] Shandong Univ, Sch Med, Key Lab Expt Teratol, Minist Educ, Jinan 250100, Shandong, Peoples R China

[4] Shandong Univ, Sch Med, Dept Mol Med & Genet, Jinan 250100, Shandong, Peoples R China

[5] Shandong Univ, Dept Breast Surg, Qilu Hosp, Jinan 250100, Shandong, Peoples R China

[6] Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

来源：

ONCOTARGET | 2014年 / 5卷 / 21期

基金：

中国国家自然科学基金;

关键词：

miR-145; MTDH; p53; HGSOC; metastasis; ELEVATED GENE-1 AEG-1; BREAST-CANCER; C-MYC; CELLS; P53; MODULATION; EXPRESSION; APOPTOSIS; CHEMORESISTANCE; ANGIOGENESIS;

D O I：

10.18632/oncotarget.2522

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

High-grade serous ovarian carcinoma (HGSOC), the most common and aggressive subtype of epithelial ovarian cancer, is characterized by TP53 mutations and genetic instability. Using miRNA profiling analysis, we found that miR-145, a p53 regulated miRNA, was frequently down-regulated in HGSOC. miR-145 down-regulation was further validated in a large cohort of HGSOCs by qPCR. Overexpression of miR-145 in ovarian cancer cells significantly suppressed proliferation, migration and invasion in vitro and inhibited tumor growth and metastasis in vivo. Metadherin (MTDH) was subsequently identified as a direct target of miR-145, and was found to be significantly up-regulated in HGSOC. Furthermore, overexpression of MTDH rescued the inhibitory effects of miR-145 in ovarian cancer cells. Finally, we found that high level of MTDH expression correlated with poor prognosis of HGSOC. Therefore, lack of suppression of MTDH by miR-145 when p53 is dysfunctional leads to increased tumor growth and metastasis of HGSOC. Our study established a new link between p53, miR-145 and MTDH in the regulation of tumor growth and metastasis in HGSOC.

引用

页码：10816 / 10829

页数：14

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