MicroRNA-576-3p Inhibits Proliferation in Bladder Cancer Cells by Targeting Cyclin D1

Abstract

MicroRNAs (miRNAs) are small, endogenous RNAs that play important gene-regulatory roles by binding to the imperfectly complementary sequences at the 3-UTR of mRNAs and directing their gene expression. Here, we first discovered that miR-576-3p was down-regulated in human bladder cancer cell lines compared with the non-malignant cell line. To better characterize the role of miR-576-3p in bladder cancer cells, we over-expressed or down-regulated miR-576-3p in bladder cancer cells by transfecting with chemically synthesized mimic or inhibitor. The overexpression of miR-576-3p remarkably inhibited cell proliferation via G1-phase arrest, and decreased both mRNA and protein levels of cyclin D1 which played a key role in G1/S phase transition. The knock-down of miR-576-3p significantly promoted the proliferation of bladder cancer cells by accelerating the progression of cell cycle and increased the expression of cyclin D1. Moreover, the dual-luciferase reporter assays indicated that miR-576-3p could directly target cyclin D1 through binding its 3-UTR. All the results demonstrated that miR-576-3p might be a novel suppressor of bladder cancer cell proliferation through targeting cyclin D1.

CCND1, NOP14 and DNMT3B are involved in miR‐502‐5p–mediated inhibition of cell migration and proliferation in bladder cancer

“…in BCa have been identified. 9,33 In our research, we found that miR-502-5p could regulate cell proliferation by targeting CCND1…”

“…Previous work has shown that CCND1 plays a key role in regulating the cell cycle of BCa cells, 9 and downregulation of CCND1 induced revealed that the expression of CCND1 was markedly reduced in bladder cancer ( Figure S3G). Consequently, CCND1, targeted by miR-502-5p, can regulate cell proliferation in BCa cells.…”

“…7 In addition, we previously confirmed the tumour-suppressing role of a series of miRNAs, including miR-22, miR-148a-3p, miR-182-5p, miR-320c, miR-323a-3p, miR-409, miR-433 and miR-576, which are involved in regulating oncogenicity and progression of BCa. [8][9][10][11][12][13][14][15] MiR-502-5p is located at Xp11. 23 and has been reported to be associated with the tumorigenicity and progression of breast cancer, 16 colon cancer, 17 liver cancer 18 and non-Hodgkin lymphoma.…”

MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway

“…Emerging discoveries of disordered miRNAs have been reported to accelerate the progression and metastasis of cancer, including BCa. Our team has previously identified a series of miRNAs, including miR-26a, miR-101, miR-124-3p, miR-320c, miR-409-3p, miR-490-5p, miR-576-3p, miR-433, miR-148a and miR-323a-3p, involved in the progression of BCa [9][10][11][12][13][14][15][16][17][18].…”

miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer

“…5, 6 In our previous studies, we identified a series of miRNAs involved in bladder cancer proliferation, migration and invasion, including miR-26a, miR-101, miR-124-3p, miR-320c, miR-409-3p, miR-490-5p, miR-433 and miR-576-3p. 7, 8, 9, 10, 11, 12, 13, 14 However, the biological function of miRNAs in bladder cancer is still unclear.…”