RETRACTED ARTICLE: MicroRNA-30d promotes angiogenesis and tumor growth via MYPT1/c-JUN/VEGFA pathway and predicts aggressive outcome in prostate cancer

Abstract

BackgroundEven though aberrant expression of microRNA (miR)-30d has been reported in prostate cancer (PCa), its associations with cancer progression remain contradictory. The aim of this study was to investigate clinical significance, biological functions and underlying mechanisms of miR-30d deregulation in PCa.MethodsInvolvement of miR-30d deregulation in malignant phenotypes of PCa was demonstrated by clinical sample evaluation, and in vitro and in vivo experiments. The mechanisms underlying its regulatory effect on tumor angiogenesis were determined.ResultsmiR-30d over-expression was observed in both PCa cells and clinical specimens. High-miR-30d was distinctly associated with high pre-operative PSA and Gleason score, advanced clinical and pathological stages, positive metastasis and biochemical recurrence (BCR), and reduced overall survival of PCa patients. Through gain- and loss-of-function experiments, we found that miR-30d promoted PCa cell proliferation, migration, invasion, and capillary tube formation of endothelial cells, as well as in vivo tumor growth and angiogenesis in a mouse model. Simulation of myosin phosphatase targeting subunit 1 (MYPT1), acting as a direct target of miR-30d, antagonized the effects induced by miR-30d up-regulation in PCa cells. Notably, miR-30d/MYPT1 combination was identified as an independent factor to predict BCR of PCa patients. Furthermore, miR-30d exerted its pro-angiogenesis function, at least in part, by inhibiting MYPT1, which in turn, increased phosphorylation levels of c-JUN and activated VEGFA-induced signaling cascade in endothelial cells.ConclusionsmiR-30d and/or its target gene MYPT1 may serve as novel prognostic markers of PCa. miR-30d promotes tumor angiogenesis of PCa through MYPT1/c-JUN/VEGFA pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0615-x) contains supplementary material, which is available to authorized users.

A novel lncRNA‐LINC01116 regulates tumorigenesis of glioma by targeting VEGFA

“…S3A). VEGFA has been ever reported to be upregulated in many tumor tissues and plays an important role in tumor cell proliferation, migration, invasion and tumor angiogenesis . Therefore, these data suggest that the contribution of LINC01116 knockdown to the inhibition of tumorigenesis, metastasis and angiogenesis in glioma might be through downregulating the expression of VEGFA.…”

“…VEGFA has been ever reported to be upregulated in many tumor tissues and plays an important role in tumor cell proliferation, migration, invasion and tumor angiogenesis. [35][36][37][38] Therefore, these data suggest that the contribution of LINC01116 knockdown to the inhibition of tumorigenesis, metastasis and angiogenesis in glioma might be through downregulating the expression of VEGFA. Thus, VEGFA may represent an important downstream effector of LINC01116 and potentially mediate this lncRNA effect on tumorigenesis, metastasis and angiogenesis in glioma.…”

Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma

“…Meanwhile, VEGFA was also found to be markedly upregulated in other tumours. The overexpression of VEGFA is a powerful predictor of overall survival and progression for some cancers, including breast cancer, prostate cancer, lung cancer and glioma [20][21][22][23][24]. Additionally, VEGFA was also demonstrated to increase the motility of PDAC cells [25].…”

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

“…4). The over-expression of miR-30d is thus associated with advanced cancer progression and an unfavorable prognosis [114]. After IR, miR-30d became decreased in PC-3 cells [41] and it was therefore suggested that miR-30d may increase the efficacy of radiotherapy.…”