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Tumour Biol. 2016 Oct;37(10):14141-14151. Epub 2016 Aug 14.

hsa-miR-135a-1 inhibits prostate cancer cell growth and migration by targeting EGFR.

Xu B1,2, Tao T1,2, Wang Y1,2, Fang F3, Huang Y1,2, Chen S1, Zhu W1, Chen M4,5.

Author information

1
Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China.
2
Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
3
Department of Immunology, Bengbu Medical College, Bengbu, China.
4
Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China. mingchenseu@126.com.
5
Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. mingchenseu@126.com.

Abstract

Prostate cancer is one of the leading causes of death in men worldwide. Differentially expressed microRNAs (miRNAs) are associated with metastatic prostate cancer. However, their potential roles for affecting prostate cancer initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs in human metastatic prostate cancer tissues. We further validated our miRNA expression data using two large, independent clinical prostate cancer datasets from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA). Our data support a model in which hsa-miR-135-1 acts as a potential tumor suppressor in metastatic prostate cancer. First, its downregulation was positively correlated with late TNM stage, high Gleason score, and adverse prognosis. Second, cell growth, cell cycle progression, cell migration and invasion, and xenograft tumor formation were dramatically inhibited by miR-135a overexpression. Third, in the microarray gene expression data analysis using Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, Ingenuity Pathway Analysis (IPA), and Oncomine concept analysis, we showed that miR-135a targets multiple oncogenic pathways including epidermal growth factor receptor (EGFR), which we verified using functional experimental assays. These results help advance our understanding of the function of miRNAs in metastatic prostate cancer and provide a basis for further clinical investigation.

KEYWORDS:

EGFR; Metastasis; Prostate cancer; miRNA

PMID:
27524492
DOI:
10.1007/s13277-016-5196-6
[Indexed for MEDLINE]

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