Microrna 138上调与人类前列腺癌细胞CCND1基因表达水平降低和促进细胞死亡相关

IF 1.4 Q4 PHARMACOLOGY & PHARMACY
Nasrin Haghighi-Najafabadi, Shima Fayaz, Mahboubeh Berizi, Ghazal Haddad, Pezhman Fard-Esfahani
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引用次数: 0

摘要

背景:本研究旨在发现miR-138 (microRNA 138)在前列腺癌(PCa)中的表达谱、增殖及其相关调控机制的意义。方法:采用RT-qPCR (Quantitative reverse transcriptpolymerase chain reaction,定量逆转录聚合酶链反应)检测35例前列腺组织中miR138的表达水平。进行生物信息学分析,寻找miR-138的靶基因;选择ABL1 (ABL原癌基因1,非受体酪氨酸激酶)、CCND1(细胞周期蛋白D1)、CCND3(细胞周期蛋白D3)、VIM(波形蛋白)、TWIST1(扭曲家族bHLH转录因子1)、HIF1A(缺氧诱导因子1亚基α)和TERT(端粒酶逆转录酶)基因。然后,利用RT-qPCR和荧光素酶报告基因检测研究miR-138和CCND1在PCa进展中的生物学作用。最后,使用MTT(3-(4,5 -二甲基噻唑-2-酰基)- 2,5 -二苯基溴化四唑,Sigma,德国)检测分析miR-138对PCa细胞系增殖的过表达。结果:RT-qPCR显示miR-138在PCa组织和细胞系中表达下调。生物信息学分析和RT-qPCR分析表明,CCND1表达水平与miR-138在PCa组织和PC3细胞系中呈负相关。此外,根据荧光素酶报告基因检测结果预测CCND1是PC3细胞系miR138的靶基因。实质上,miR138-5p mimic的过表达可以抑制PC3细胞系中CCND1基因的表达水平。最后,过表达miR-138抑制了PC3和DU-145细胞的增殖能力。结论:我们的研究引入了miR-138作为CCND1在PCa进展中的负调节因子,对PCa细胞系的增殖率有抑制作用。这一调控机制可用于基于mirna的治疗方法的设计和靶点选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Microrna 138 Upregulation is Associated with Decreasing Levels of CCND1 Gene Expression and Promoting Cell Death in Human Prostate Cancer Cell Lines
Background: This research intended to discover the significance of miR-138 (microRNA 138) on the expression profile, proliferation, and the associated regulatory mechanisms in prostate cancer (PCa). Methods: Thirty-five specimens of prostate were studied to evaluate the expression level of miR138 by RT-qPCR (Quantitative reverse transcription polymerase chain reaction). Bioinformatics analysis was performed to search for the target genes of miR-138; and ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase), CCND1 (cyclin D1), CCND3 (cyclin D3), VIM (vimentin), TWIST1 (twist family bHLH transcription factor 1), HIF1A (hypoxia-inducible factor 1 subunit alpha), and TERT (telomerase reverse transcriptase) genes were selected. Then, the biological role of miR-138 and CCND1 in the progression of PCa was investigated using RT-qPCR and luciferase reporter gene assay. Finally, overexpression of miR-138 on the proliferation in PCa cell lines was analyzed using the MTT (3-(4, 5-dimethylthiazol-2-Yl)-2, 5-diphenyltetrazolium bromide, Sigma, Germany) assay. Results: RT-qPCR showed that the expression of miR-138 downregulated in PCa tissues and cell lines. Bioinformatics analysis and RT-qPCR assay demonstrated that CCND1 expression level was negatively correlated with miR-138 in PCa tissues and the PC3 cell line. Moreover, CCND1 was predicted to be the target gene of miR138 in the PC3 cell line based on the results of luciferase reporter gene assay. Substantially, over-expression of miR138-5p mimic could inhibit the expression level of CCND1 gene in PC3 cell lines. Lastly, over-expression of miR-138 inhibited the proliferative capacities in PC3 and DU-145 cells. Conclusion: Our research introduces miR-138 as a negative regulator of CCND1 in the progression of PCa with an inhibitory impact on the proliferation rate of PCa cell lines. This regulatory mechanism could be utilized for the design and target selection of remedial miRNA-based approaches.
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来源期刊
Pharmaceutical Sciences
Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-
CiteScore
2.60
自引率
5.90%
发文量
38
审稿时长
4 weeks
期刊介绍: Pharmaceutical Sciences provides a forum for the publication of original research articles, reviews, short communications, and editorials (by invitation only) in all areas of pharmaceutical sciences, including these topics: Clinical Pharmacy Medicinal and Pharmaceutical Chemistry Pharmaceutical Analysis Pharmaceutics Pharmacognosy Pharmacology and Toxicology Pharmaceutical Biotechnology Pharmaceutical Nanotechnology Pharmacoeconomy Radiopharmacy Water, Food, Drug and Cosmetic Control.
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