miR-188-5p inhibits tumour growth and metastasis in prostate cancer by repressing LAPTM4B expression

Abstract

Elucidation of the molecular targets and pathways regulated by the tumour-suppressive miRNAs can shed light on the oncogenic and metastatic processes in prostate cancer (PCa). Using miRNA profiling analysis, we find that miR-188-5p was significantly down-regulated in metastatic PCa. Down-regulation of miR-188-5p is an independent prognostic factor for poor overall and biochemical recurrence-free survival. Restoration of miR-188-5p in PCa cells (PC-3 and LNCaP) significantly suppresses proliferation, migration and invasion in vitro and inhibits tumour growth and metastasis in vivo. We also find overexpression of miR-188-5p in PC-3 cells can significantly enhance the cells' chemosensitivity to adriamycin. LAPTM4B is subsequently identified as a direct target of miR-188-5p in PCa, and is found to be significantly over-expressed in PCa. Knockdown of LAPTM4B phenotypically copies miR-188-5p-induced phenotypes, whereas ectopic expression of LAPTM4B reverses the effects of miR-188-5p. We also find that restoration of miR-188-5p can inhibit the PI3K/AKT signaling pathway via the suppression of LAPTM4B. Taken together, this is the first report unveils that miR-188-5p acts as a tumour suppressor in PCa and may therefore serve as a useful therapeutic target for the development of new anticancer therapy.

Association between LAPTM4B gene polymorphism and prostate cancer susceptibility in an Iranian population

“…Decreased expression of miR-188-5p is associated with poor prognosis in patients with PCa, which strongly suggests a potential role of miR-188-5p in suppression of PCa. 38 In summary, our findings are the first to show an association between LAPTM4B polymorphism and risk of PCa in a sample of the Iranian population. Further studies with larger sample sizes and different ethnicities are required to validate our findings.…”

“…It has been shown that miR-188-5p, which acts as a tumor suppressor, inhibits PCa cell proliferation, invasion, and migration through downregulation of LAPTM4B by directly binding to its 3 0 -UTR 38 and subsequent inhibition of the PI3K/AKT signaling pathway. Decreased expression of miR-188-5p is associated with poor prognosis in patients with PCa, which strongly suggests a potential role of miR-188-5p in suppression of PCa.…”

MicroRNA expression profiling in patients with hepatocellular carcinoma of familial aggregation and hepatitis B virus infection

“…The remaining 11 miRNAs have never been studied in liver cancer (Table III). Among the 11 differentially dysregulated miRNAs, the function of miR-374a, miR-188-5p, miR-1183, miR-454, miR-324-3p, miR-484, miR-3188, and miR-216b have been studied in human cancers (27,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43); however, the exact function of miR-4271, miR-1471 and miR-3610 remains unclear.…”

“…A previous study indicated that miR-1183 and miR-188-5p may represent specific predictors of response to chemoradiotherapy in rectal cancer (32). miR-188-5p is involved in the process of prostate cancer by regulating lysosomal protein transmembrane 4 β (LAPTM4B) (33). The downregulation of miR-188-5p is an independent prognostic factor for poor overall and biochemical recurrence-free survival rates, restoration of miR-188-5p in prostate cancer (PCa) cells significantly suppresses proliferation, migration and invasion in vitro and inhibits tumor growth and metastasis in vivo (33); Overexpression of miR-188-5p in PC-3 cells may significantly enhance the chemosensitivity of the cells to adriamycin (33).…”

“…miR-188-5p is involved in the process of prostate cancer by regulating lysosomal protein transmembrane 4 β (LAPTM4B) (33). The downregulation of miR-188-5p is an independent prognostic factor for poor overall and biochemical recurrence-free survival rates, restoration of miR-188-5p in prostate cancer (PCa) cells significantly suppresses proliferation, migration and invasion in vitro and inhibits tumor growth and metastasis in vivo (33); Overexpression of miR-188-5p in PC-3 cells may significantly enhance the chemosensitivity of the cells to adriamycin (33). The miR-188-5p/LAPTM4B/ phosphoinositide-3 kinase/protein kinase B regulatory network performs an important role in PCa progression and chemotherapeutic drug sensitivity (33).…”