Dataset Information

Loss of miR-516a-3p mediates upregulation of ABCC5 in prostate cancer and drives its progression.

ABSTRACT: To gain a comprehensive understanding of whether ABCC5 can regulate prostate cancer (PCa) progression, we performed microarray data analyses and identified that ABCC5 was drastically increased in primary PCa relative to normal samples, metastatic PCa relative to primary PCa, and castration-resistant PCa relative to hormone naïve PCa, respectively. Multivariate Cox regression analysis suggested that ABCC5 overexpression in PCa was an independent prognostic factor for both poor biochemical recurrence-free and overall survival. We demonstrated that ABCC5 knockdown significantly inhibits PCa cell proliferation, migration, and invasion in vitro and suppresses tumor growth and metastasis in vivo. We also demonstrated that miR-516a-3p was significantly downregulated in PCa. We finally demonstrated that ABCC5 was a direct target of miR-516a-3p. miR-516a-3p overexpression can phenotypically copy ABCC5 knockdown-induced phenotypes, whereas forced expression of ABCC5 can drastically reverse the inhibitory effects of miR-516a-3p. miR-516a-3p may modulate the sensitivity of cancer cells to adriamycin and docetaxel by targeting ABCC5 with important implications in the design of new therapeutic agents. Taken together, our results indicated that loss of miR-516a-3p expression and thus uncontrolled ABCC5 upregulation might drive PCa progression and influence chemosensitivity.

SUBMITTER: Zhang H

PROVIDER: S-EPMC6039062 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Loss of miR-516a-3p mediates upregulation of ABCC5 in prostate cancer and drives its progression.

Zhang Hongtuan H Lian Zhenpeng Z Sun Guangyu G Liu Ranlu R Xu Yong Y

OncoTargets and therapy 20180706

To gain a comprehensive understanding of whether ABCC5 can regulate prostate cancer (PCa) progression, we performed microarray data analyses and identified that ABCC5 was drastically increased in primary PCa relative to normal samples, metastatic PCa relative to primary PCa, and castration-resistant PCa relative to hormone naïve PCa, respectively. Multivariate Cox regression analysis suggested that ABCC5 overexpression in PCa was an independent prognostic factor for both poor biochemical recurre ...[more]

PMID: 30013366

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Project description:Accumulating evidences revealed that long noncoding RNAs (lncRNAs) have been participated in cancer malignant progression, including glioblastoma multiforme (GBM). Despite much studies have found the precise biological role in the regulatory mechanisms of GBM, however the molecular mechanisms, particularly upstream mechanisms still need further elucidated. RT-QPCR, cell transfection, western blotting and bioinformatic analysis were executed to detect the expression of EGR1, HNF1A-AS1, miR-22-3p and ENO1 in GBM. Cell proliferation assay, colony formation assay, wound healing, migration and invasion assays were performed to detect the malignant characters of GBM cells. The molecular regulation mechanism was confirmed by luciferase reporter assay, ChIP and RIP. Finally, orthotopic mouse models were established to examine the effect of HNF1A-AS1 in vivo. In the current study, we analyzed clinical samples to show that the HNF1A-AS1 expression is upregulated and associated with poor patient survival in GBM. Functional studies revealed that HNF1A-AS1 knockdown markedly inhibits malignant phenotypes of GBM cells, whereas overexpression of HNF1A-AS1 exerts opposite effect. Mechanistically, the transcription factor EGR1 forced the HNF1A-AS1 expression by directly binding the promoter region of HNF1A-AS1. Furthermore, combined bioinformatics analysis with our mechanistic work, using luciferase reporter assays and RIP, we first demonstrated that HNF1A-AS1 functions as a competing endogenous RNA (ceRNA) with miR-22-3p to regulate ENO1 expression in GBM cells. HNF1A-AS1 directly binds to miR-22-3p and significantly inhibits miR-22-3p expression, while ENO1 expression was increased. miR-22-3p inhibitor offsets the HNF1A-AS1 silencing induced suppression in malignant behaviors of GBM cells. ENO1 was verified as a direct target of miR-22-3p and its expression levels was negatively with the prognosis in GBM patients. Taken together, our study illuminated the definite mechanism of HNF1A-AS1 in promoting GBM malignancy, and provided a novel therapeutic target for further clinical application.

Dataset Information

Loss of miR-516a-3p mediates upregulation of ABCC5 in prostate cancer and drives its progression.

Publications

Loss of miR-516a-3p mediates upregulation of ABCC5 in prostate cancer and drives its progression.

Similar Datasets

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