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Targeting survivin using a combination of miR?494 and survivin shRNA has synergistic effects on the suppression of prostate cancer growth.

ABSTRACT: Castration-resistant prostate cancer (CRPC) remains an obstacle in the current treatment provided for prostate cancer (PCa). Survivin, an apoptosis inhibitor, has been found to be involved in the progression of PCa, and is a promising candidate target for CRPC therapy. Micro (mi)RNAs are involved in the progression of PCa through the regulation of multiple genes. One of the objectives of the present study was to investigate the effect of miRNA (miR)?494 on the expression of survivin, as well as on PCa growth. The present study also aimed to assess whether co-transfecting miR?494 with survivin short hairpin (sh)RNA has synergistic effects on suppressing PCa proliferation or the expression of survivin. Gene Expression Omnibus datasets with clinical PCa miRNA expression profiles were utilized to analysis the expression of miR?494 in Ca, compared with normal prostate samples. PC3 cells, a CRPC cell line, were transfected with either an miR?494 expression adenovirus, a survivin shRNA adenovirus or the two together, to examine their effect on PCa growth and the expression of survivin in vitro and in vivo. miR?494 was downregulated in PCa tissue samples and in the PC?3 cell line. miR?494 targeted survivin at the translational level in PCa. Overexpression of miR?494 and silencing survivin RNA through the use of survivin shRNA inhibited the expression of survivin and attenuated PC?3 cell growth in vitro and in vivo. Notably, co?transfecting miR?494 with survivin shRNA had synergistic effects on suppressing prostate cancer proliferation via further suppression of the expression of survivin. These results suggested that using multiple methods to inhibit the function of survivin may have improved efficacy for treating PCa.

SUBMITTER: Zhu J

PROVIDER: S-EPMC4732832 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Targeting survivin using a combination of miR‑494 and survivin shRNA has synergistic effects on the suppression of prostate cancer growth.

Zhu Jin J Sun Chenwen C Wang Liping L Xu Ming M Zang Yachen Y Zhou Yibin Y Liu Xiaolong X Tao Wei W Xue Boxin B Shan Yuxi Y Yang Dongrong D

Molecular medicine reports 20151230 2

Castration-resistant prostate cancer (CRPC) remains an obstacle in the current treatment provided for prostate cancer (PCa). Survivin, an apoptosis inhibitor, has been found to be involved in the progression of PCa, and is a promising candidate target for CRPC therapy. Micro (mi)RNAs are involved in the progression of PCa through the regulation of multiple genes. One of the objectives of the present study was to investigate the effect of miRNA (miR)‑494 on the expression of survivin, as well as ...[more]

PMID: 26718651

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Project description:Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications characterized by insulin resistance and pancreatic ?-cell dysfunction. Increasing evidence suggests that microRNAs (miRNAs) play key roles in the diverse types of diabetes, including GDM. However, the underlying mechanisms remain largely unknown. The purpose of this study is to investigate the role of microRNAs in GDM. The microarray data of dysregulated miRNAs in blood and placenta was retrieved in the GEO dataset under the accession number GSE19649. Quantitative reverse transcription PCR (qRT-PCR) was performed to analyze the expression levels of miR-494 in peripheral blood from twenty pairs of gestational diabetes (GDM) women and healthy women. Then, we investigated the effects of miR-494 on the insulin secretion of pancreatic ?-cells. Moreover, the role of this miR-494 in regulating the proliferation and apoptosis of pancreatic ?-cells were determined by MTT assay and flow cytometry, respectively in INS1 cells transfected with a miR-494 mimic or inhibitor. In addition, the direct target of miR-494 was confirmed using 3' untranslated region (UTR) luciferase reporter assay. Our data demonstrated that the miR-494 level was significantly decreased in the blood of GDM patients, and the low level was associated with a high concentration of blood glucose. Furthermore, overexpression of miR-494 improved pancreatic ?-cell dysfunction by enhancing insulin secretion and total insulin content, inducing cell proliferation, and inhibiting cell apoptosis, whereas miR-494 knockdown exhibited decreased insulin secretion and proliferation, as well as stimulated apoptosis. In addition, phosphatase and tensin homolog (PTEN) which has been shown to play a pivotal role in apoptosis, was proved to be a direct target of miR-494 in pancreatic ?-cells. More importantly, siRNA-induced downregulation of PTEN reversed the effects of miR-494 knockdown on insulin secretion, cell proliferation, and apoptosis of pancreatic ?-cells.

Dataset Information

Targeting survivin using a combination of miR?494 and survivin shRNA has synergistic effects on the suppression of prostate cancer growth.

Publications

Targeting survivin using a combination of miR‑494 and survivin shRNA has synergistic effects on the suppression of prostate cancer growth.

Similar Datasets

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