Role of MicroRNA-21 in Prostate Cancer Progression and Metastasis: Molecular Mechanisms to Therapeutic Targets.

The role of noncoding RNA has made remarkable progress in understanding progression, metastasis, and metastatic castration-resistant prostate cancer (mCRPC). A better understanding of the miRNAs has enhanced our knowledge of their targeting mainly at the therapy level in solid tumors, such as prostate cancer (PCa). microRNAs (miRNAs) belong to a class of endogenous RNA that deficit encoded proteins. Therefore, the role of miRNAs has been well-coined in the progression and development of PCa. miR-21 has a dual nature in its work both as a tumor suppressor and oncogenic role, but most of the recent studies showed that miR-21 is a tumor promoter and also is involved in castration-resistant prostate cancer (CRPC). Upregulation of miR-21 suppresses programmed cell death and inducing metastasis and castration resistant in PCa. miR-21 is involved in the different stages, such as proliferation, angiogenesis, migration, and invasion, and plays an important role in the progression, metastasis, and advanced stages of PCa. Recently, various studies directly linked the role of high levels of miR-21 with a poor therapeutic response in the patient of PCa. In the present review, we have explained the molecular mechanisms/pathways of miR-21 in PCa progression, metastasis, and castration resistant and summarized the role of miR-21 in diagnosis and therapeutic levels in PCa. In addition, we have spotlighted the recent therapeutic strategies for targeting different stages of PCa.

Singh VK ，Rajak N ，Singh Y ，Singh AK ，Giri R ，Garg N ... -  《-》

Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer.

Prostate cancer (PCa) is a leading cause of cancer-related death. Upon androgen-deprivation therapy, the disease may progress further to castration-resistant PCa (CRPC) with a poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs, which play crucial roles in gene regulation. The aim of our study is to find CRPC-associated miRNAs and to evaluate their functional role. In this study, 23 benign prostatic hyperplasia (BPH), 76 primary PCa, and 35 CRPC specimens were included. Total RNA extracted from tissue sections was used for miRNA profiling on the Affymetrix GSC 3000 platform. Subsequently, stem-loop RT-qPCR analysis was performed to validate the expression levels of selected miRNAs. PCa cell lines were transfected with miRNA mimics or inhibitors to evaluate the effects on cell proliferation, cell migration and cell invasion. In our profiling study, several miRNAs were found to be deregulated in CRPC compared to primary PCa tissue, of which miR-205 (- 4.5-fold; p = 0.0009), miR-92b (- 3.1 fold; p < 0.0001) were downregulated and miR-3195 (5.6-fold; p < 0.0001), miR-3687 (8.7-fold; p = 0.0006) and miR-4417 (5.0-fold; p = 0.0005) were most upregulated. While KLK3, miR-21 and miR-141 expression levels in androgen-treated VCaP and LNCaP cells were increased, the expression levels of miR-3687 and miR-4417 were reduced. None of the miRNAs were androgen-regulated in the AR-negative PC3 cell line. Overexpression of miR-3687 reduced cell migration and cell invasion, whilst miR-3195 enhanced cell migration. We have identified several novel deregulated miRNAs in CRPC tissue, including two microRNAs that are potentially involved in tumor invasion. Our data support the hypothesized involvement of miRNAs in PCa tumorigenesis and progression to CRPC. The applicability of these miRNAs as novel biomarkers for CRPC remains to be further investigated.

Rönnau CGH ，Fussek S ，Smit FP ，Aalders TW ，van Hooij O ，Pinto PMC ，Burchardt M ，Schalken JA ，Verhaegh GW ... -  《-》

MicroRNA expression signature of castration-resistant prostate cancer: the microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker.

Goto Y ，Kojima S ，Nishikawa R ，Kurozumi A ，Kato M ，Enokida H ，Matsushita R ，Yamazaki K ，Ishida Y ，Nakagawa M ，Naya Y ，Ichikawa T ，Seki N ... -  《-》

Long noncoding RNA LINC00963 induces NOP2 expression by sponging tumor suppressor miR-542-3p to promote metastasis in prostate cancer.

Sun F ，Wu K ，Yao Z ，Mu X ，Zheng Z ，Sun M ，Wang Y ，Liu Z ，Zhu Y ... -  《Aging-US》

Involvement of aberrantly activated HOTAIR/EZH2/miR-193a feedback loop in progression of prostate cancer.

Ling Z ，Wang X ，Tao T ，Zhang L ，Guan H ，You Z ，Lu K ，Zhang G ，Chen S ，Wu J ，Qian J ，Liu H ，Xu B ，Chen M ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》