Abstract

BackgroundEmerging evidence continues to highlight the significant role of microRNAs (miRNAs) in the regulation of cancer growth and metastasis. Herein, the current study aimed to elucidate the role of exosomal miR-183 in prostate cancer development.MethodsInitially, public microarray-based gene expression profiling of prostate cancer was employed to identify differentially expressed miRNAs. The putative target gene TPM1 of miR-183 was subsequently predicted, followed by the application of a luciferase reporter assay and examination of the expression patterns in prostate cancer patients and cell lines. The effects of miR-183 and TPM1 on processes such as cell proliferation, invasion and migration were evaluated using in vitro gain- and loss-of-function experiments. The effect of PC3 cells-derived exosomal miR-183 was validated in LNCaP cells. In vivo experiments were also performed to examine the effect of miR-183 on prostate tumor growth.ResultsHigh expression of miR-183 accompanied with low expression of TPM1 was detected in prostate cancer. Our data indicated that miR-183 could target and downregulate TPM1, with the overexpression of miR-183 and exosomal miR-183 found to promote cell proliferation, migration, and invasion in prostate cancer. Furthermore, the tumor-promoting effect of exosome-mediated delivery of miR-183 was subsequently confirmed in a tumor xenograft model.ConclusionsTaken together, the key findings of our study demonstrate that prostate cancer cell-derived exosomal miR-183 enhance prostate cancer cell proliferation, invasion and migration via the downregulation of TPM1, highlighting a promising therapeutic target against prostate cancer.

Highlights

  • Emerging evidence continues to highlight the significant role of microRNAs in the regulation of cancer growth and metastasis

  • A significant amount of research attention has been recently drawn to exosomal miRNAs owing to their potential as biomarkers for cancer investigation including exosomal miR-129 and miR-375 in castrationresistant prostate cancer [9]. miRNAs represent a class of small, endogenous non-coding RNA that have been shown to negatively regulate gene expression by means of suppressing translation and facilitating the degradation of target mRNA [10]. miRNAs have been reported to possess the ability to influence a wide variety of biological pathways [11]. miRNAs have been reported to play a role in various cellular processes such as cell-cycle regulation, differentiation, apoptosis, and migration, whose alteration has been implicated in the development and progression of various cancers [12]

  • The expression of TPM1 in prostate cancer based on The Cancer Genome Atlas (TCGA) and in normal samples was analyzed by GEPIA (Gene Expression Profiling Interactive Analysis)

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Summary

Introduction

Emerging evidence continues to highlight the significant role of microRNAs (miRNAs) in the regulation of cancer growth and metastasis. The current study aimed to elucidate the role of exosomal miR-183 in prostate cancer development. The dysregulation of exosomal miRNAs has been implicated in metastatic prostate cancer [7]. Exosomal miRNAs represent promising potential biomarkers for the development of metastatic treatment for prostate cancer. MiRNAs have been reported to play a role in various cellular processes such as cell-cycle regulation, differentiation, apoptosis, and migration, whose alteration has been implicated in the development and progression of various cancers [12]. Findings obtained from a study suggests an under-expressed miRNA, microRNA-183 (miR-183) contributes to the regulation of zinc homeostasis whose decrease was a feature of prostate cancer [13]. It might be possible that miR-183 may contribute to pathogenesis of prostate cancer

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