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miR-582-5p的上调通过靶向人子宫内膜癌中的AKT3来调节细胞增殖和凋亡。

Upregulation of miR-582-5p regulates cell proliferation and apoptosis by targeting AKT3 in human endometrial carcinoma.

作者信息

Li Lingling, Ma Li

机构信息

Department of Gynecology of Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, PR China.

出版信息

Saudi J Biol Sci. 2018 Jul;25(5):965-970. doi: 10.1016/j.sjbs.2018.03.007. Epub 2018 Mar 10.

DOI:10.1016/j.sjbs.2018.03.007
PMID:30108448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6088104/
Abstract

The human endometrial carcinoma is one of the most common female malignancies, and there is an urgent requirement to explore new therapeutic strategies. There is accumulating evidence that microRNAs (miRNAs) can serve as potential diagnostic and prognostic biomarkers for various types of cancer, but the significance of miR-582-5p still remains largely unknown in the endometrial carcinoma. The aims of this study were to understand and identify the influence of miR-582-5p on the proliferation and apoptosis of human endometrial carcinoma and its relevant mechanism. First, quantitative real-time PCR (qRT-PCR) was used to detect miR-582-5p and AKT3 expression in human tissue samples and cells. Then, CyQuant assay and 2D colony assay were employed to evaluate cell proliferation. Western blotting was used to determine protein expression. Subsequently, the luciferase reporter assay was used to identify the target of miR-582-5p. Finally, Annexin V assay was used to detect cell apoptosis. We found that miR-582-5p expression was significantly decreased in human endometrial carcinoma tissues, and miR-582-5p upregulation in human endometrial carcinoma cells inhibit cell proliferation and promote apoptosis. Moreover, AKT3 was validated as a target of miR-582-5p and AKT3 expression was inversely correlated with miR-582-5p expression. Besides, AKT3 upregulation efficiently abrogates the effect of miR-582-5p on the cells. These results demonstrated that miR-582-5p regulates cell proliferation and apoptosis in human endometrial carcinoma via AKT3. Thus, miR-582-5p represents a potential therapeutic target in human endometrial carcinoma meriting further investigation.

摘要

子宫内膜癌是女性最常见的恶性肿瘤之一,迫切需要探索新的治疗策略。越来越多的证据表明,微小RNA(miRNA)可作为各种癌症潜在的诊断和预后生物标志物,但miR-582-5p在子宫内膜癌中的意义仍基本未知。本研究的目的是了解和确定miR-582-5p对人子宫内膜癌增殖和凋亡的影响及其相关机制。首先,采用定量实时PCR(qRT-PCR)检测人组织样本和细胞中miR-582-5p和AKT3的表达。然后,采用CyQuant法和二维集落法评估细胞增殖。蛋白质印迹法用于测定蛋白质表达。随后,采用荧光素酶报告基因检测法鉴定miR-582-5p的靶标。最后,采用膜联蛋白V检测法检测细胞凋亡。我们发现,miR-582-5p在人子宫内膜癌组织中的表达显著降低,人子宫内膜癌细胞中miR-582-5p的上调抑制细胞增殖并促进凋亡。此外,AKT3被确认为miR-582-5p的靶标,且AKT3的表达与miR-582-5p的表达呈负相关。此外,AKT3的上调有效地消除了miR-582-5p对细胞的影响。这些结果表明,miR-582-5p通过AKT调节人子宫内膜癌的细胞增殖和凋亡。因此,miR-582-5p是子宫内膜癌潜在的治疗靶点,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/6088104/124fbf16375c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/6088104/07a8f229648f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/6088104/654f5f974b23/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/6088104/e99fcfd45c88/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/6088104/124fbf16375c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/6088104/07a8f229648f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/6088104/654f5f974b23/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/6088104/e99fcfd45c88/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/6088104/124fbf16375c/gr4.jpg

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