Prostate cancer cell proliferation is suppressed by microRNA‑3160‑5p via targeting of F‑box and WD repeat domain containing 8

Abstract

Abstract. MicroRNAs (miRNAs/miRs), which are endogenous non-coding single-stranded RNAs 19-25 nucleotides in length, regulate gene expression by blocking translation or transcription repression. The present study revealed that miR-3160-5p was widely expressed in prostate cancer cells by reverse transcription-quantitative polymerase chain reaction. There was a negative association between the expression of miR-3160-5p and F-box and WD repeat domain containing 8 (Fbxw8) in prostate cancer DU145 cells. A luciferase activity assay was used to verify that Fbxw8 is the target of miR-3160-5p. In the present study, using MTT assay and cell cycle analysis, it was demonstrated that DU145 cell proliferation was repressed and the cell cycle was arrested in the G 2 /M cell cycle phase with upregulation of miR-3160-5p. Subsequent studies demonstrated that miR-3160-5p regulated the progression of the cell cycle in DU145 prostate cancer cells when the expression levels of phosphorylated cell division cycle (CDC)2, CDC25C and cyclin B1 were directly inhibited. Taken together, these findings revealed the mechanism underlying the role of miR-3160-5p in regulating the proliferation of DU145 cells and indicated that miR-3160-5p may serve as a promising novel therapeutic tool for prostate cancer.

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

“…Studies have shown that Fbxw8 is involved in cancer cell growth via proteolysis 89 . Consistent with the finding that CUL7 participates in the promotion of migration and invasion in choriocarcinoma cells 55 , Fbxw8 expression levels are increased in human trophoblast cell lines, including choriocarcinoma 90 , and regulate cell proliferation 23 , 89 – 91 (Fig. 2 ), while the effect of Fbxw8 on the tumor migration, invasion, and metastasis remains unclear, indicating that more research about the impact of Fbxw8 on cancer progression is needed.…”

“…Numerous studies have demonstrated that miRNAs also contribute to the initiation and development of various human cancers 126 , 127 . miR-218 may be an effective therapeutic target for human choriocarcinoma cell growth 128 and miR-3160-5p suppressed the proliferation of DU145 prostate cancer cells and was negatively related to the expression of Fbxw8 91 . For Fbxw11, miR-106b-25, and miR-182 regulated the cell proliferation, migration, and invasion in NSCLC by targeting Fbxw11 96 , 97 .…”

Five Circular RNAs in Metabolism Pathways Related to Prostate Cancer

“…Hsa_circ_0003970 and hsa_circ_0005848 interacted with miRNA-204-5p, which is a tumor suppressor that promotes apoptosis by targeting BCL2 in PCa cells ( Lin et al, 2017 ). Hsa_circ_0005848 and hsa_circ_0006754 related miR-3160-5p is a PCa cell proliferation suppressor that targets the F-box protein ( Lin et al, 2018 ). MiR-548 acts as an anti-oncogenic factor that inhibits the phosphoinositide three-kinase (PI3K)/AKT signaling pathway in lung cancer and is associated with high-risk Gleason scores in PCa ( Shi et al, 2015 ).…”

FBXW8 regulates G1 and S phases of cell cycle progression by restricting β‐TrCP1 function

“…FBXW8 promotes proliferation of colon carcinoma through directing the proteasomal degradation of cyclin D1 during S phase [33]. Thus, FBXW8 regulates multiple cell cycle regulators to promote cancer; however, several miRNAs were found to be involved in restricting the expression level of FBXW8 in cancer [53,54]. In contrast to oncogenic role, FBXW8 also acts as tumor suppressor through promoting degradation of IRS‐1 [55].…”

“…It is reported that FBXW8 is involved in promoting many cancers including choriocarcinoma, prostate, pancreatic, and colon cancer [33,52,53]. In choriocarcinoma, FBXW8 promotes malignancy through controlling the expression levels of CDK1, CDK2, cyclin A, cyclin B, and p27 [52].…”