Abstract
Increasing reports have demonstrated that aberrant expression of microRNAs (miRNAs) is found in multiple human cancers. Many studies have shown that down-regulated level of miR-30a is in a variety of cancers including prostate cancer (PCa). However, the precise mechanisms of miR-30a in PCa have not been well explored. In this study, we investigated the biological functions and molecular mechanism of miR-30a in PCa cell lines, discussing whether it could be a therapeutic biomarker of PCa in the future. We found that miR-30a is down-regulated in PCa tissues and cell lines. Moreover, the low level of miR-30a was associated with increased expression of SIX1 in PCa tissues and cell lines. Up-regulation of miR-30a significantly inhibited proliferation of PCa cells. In addition, invasion of PCa cells was suppressed by overexpression of miR-30a. However, down-regulation of miR-30a promoted cell growth and invasion of PCa cells. Bioinformatics analysis predicted that the SIX1 was a potential target gene of miR-30a. Next, luciferase reporter assay confirmed that miR-30a could directly target SIX1. Consistent with the effect of miR-30a, down-regulation of SIX1 by siRNA inhibited proliferation and invasion of PCa cells. Overexpression of SIX1 in PCa cells partially reversed the effect of miR-30a mimic. In conclusion, introduction of miR-30a dramatically inhibited proliferation and invasion of PCa cells by down-regulating SIX1 expression, and that down-regulation of SIX1 was essential for inhibition of cell growth and invasion of PCa cells by overexpression of miR-30a.
Highlights
Prostate cancer (PCa), one of the most prevalent malignancies, is a common male malignancy and causes an increase in mortality worldwide every year [1]
We demonstrated that the level of miR-30a was frequently down-regulated in prostate cancer (PCa) tissues and cell lines, which was consistent with previous study [24]
Our results showed that the level of miR-30a was down-regulated in these five PCa cell lines compared to that in PNT2 (Fig. 1a)
Summary
Prostate cancer (PCa), one of the most prevalent malignancies, is a common male malignancy and causes an increase in mortality worldwide every year [1]. Since the growth and metastasis of PCa cells is rapid, PCa is still unmanageable [2]. Cancer therapies are well developed over the past decades, there is still short of effective therapeutic method for PCa [3]. The precise molecular mechanisms of the pathogenesis of PCa are unclear, which seriously dampens the development of effective treatment for PCa. there is an urgent need to gain a better understanding of PCa pathogenesis for improving the present therapeutic management of PCa. MicroRNAs (miRNAs) are a subset of small (about 22 nucleotides in length), non-coding RNAs [4] which can degrade mRNA or suppress their translation by binding to complementary sequences in the 30UTRs of targeted mRNAs [5, 6]. These findings provide a strong basis for the importance of miRNAs
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