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

Abstract

Purpose 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. Methods 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. Results 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. Conclusion 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.

Advances in the Current Understanding of the Mechanisms Governing the Acquisition of Castration-Resistant Prostate Cancer

“…These ncRNAs can play diverse roles as the regulators of processes such as differentiation, metabolic activity, and apoptosis [ 174 , 175 , 176 ]. The dysregulation of specific ncRNAs can contribute to the development and progression of PCA, with many studies having thus explored patterns of differential ncRNA expression during the different stages of PCA [ 175 , 176 , 177 , 178 , 179 ]. An increasing number of ncRNAs have been identified using high-throughput RNA sequencing (RNA-seq) technologies, playing important roles in the development of CRPC through various mechanisms [ 180 ].…”

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021

“…At present, one of the treatments for metastatic PCa is androgen-deprivation therapy (ADT), but many patients develop resistance to ADT and progressed into ADT-resistant prostate cancer (CRPC). By comparing the differentially expressed miRNAs in tumor tissues between CRPC and primary PCa patients, Ronnau et al obtained the combination of three miRNAs (miRNA-205, miRNA-3195 and miRNA-4417), which could be used as a potential biomarker for differentiating CRPC from primary PCa [ 139 ]. The abnormal expression of miRNAs in the tissues of PCa patients can be used to determine patient prognosis as well, and the prognosis is directly related to the clinical therapeutic effect and metastasis of PCa.…”

Differential Expression of miRNAs Contributes to Tumor Aggressiveness and Racial Disparity in African American Men with Prostate Cancer

“…miR-5100, miR-199b-3p, miR-26b-5p, and miR-98-5p were associated with the risk of prostate cancer [ 10 , 11 , 12 ]. In addition, miR-26b-5p, miR-4732-3p, miR-181A, miR-205, miR-3195, and miR-4417 were suggested as potential biomarkers for differentiating advanced cases from an early stage of prostate cancer [ 11 , 13 , 14 ]. miRNA-532-5p, miR-17-5p, and miR-199b-3p were proposed as biomarkers for prognosis [ 12 , 15 , 16 ].…”