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恢复miR-193a-5p和miR-146a-5p的表达通过靶向MDM2/p53诱导结直肠癌的G1期阻滞。

Restoration of miR-193a-5p and miR-146 a-5p Expression Induces G1 Arrest in Colorectal Cancer through Targeting of MDM2/p53.

作者信息

Noorolyai Saeed, Baghbani Elham, Aghebati Maleki Leili, Baghbanzadeh Kojabad Amir, Shanehbansdi Dariush, Khaze Shahgoli Vahid, Mokhtarzadeh Ahad, Baradaran Behzad

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. Introduction.

出版信息

Adv Pharm Bull. 2020 Jan;10(1):130-134. doi: 10.15171/apb.2020.017. Epub 2019 Dec 11.

Abstract

Colorectal cancer (CRC) remains a universal and lethal cancer owing to metastatic and relapsing disease. Currently, the role of microRNAs has been checked in tumorigeneses. Numerous studies have revealed that between the tumor suppressor miRNAs, the reduced expression of miR-146a-5p and -193a-5p in several cancers including CRC tissues are related with tumor progression and poor prognosis of patients. The purpose of this study is to examine the role of miR-146 a-5p and -193 a-5p in CRC cell cycle progression. The miR-193a-5p and -146 a-5p mimics were transfected into HT-29 CRC cells via jetPEI transfection reagent and their impact was assessed on p53, cyclin B, and NF-kB gene expression. The inhibitory effect of these miRNAs on cell cycle was assessed by flow cytometry. The consequence of miR-193a-5p and miR-146 a-5p on the protein expression level of Murine double minute 2 (MDM2) was assessed by western blotting. miR193a-5p and -146a-5p regulated the expression of MDM2 protein and p53, cyclin B, and NF-kB gene expression in CRC cells. Treatment of HT-29 cells with miRNA-146a-5p and -193a-5p induced G1 cell cycle arrest. The findings of our study suggest that miR146a-5p and -193a-5p may act as a potential tumor suppressor by their influence on cell cycle progression in CRC cells. Thus, miRNA-146a-5p and -193a-5p restoration may be recommended as a potential therapeutic goal in the treatment of CRC patients.

摘要

由于转移性和复发性疾病,结直肠癌(CRC)仍然是一种普遍存在且致命的癌症。目前,微小RNA在肿瘤发生中的作用已得到研究。大量研究表明,在肿瘤抑制性微小RNA中,包括CRC组织在内的几种癌症中miR-146a-5p和-193a-5p的表达降低与肿瘤进展及患者预后不良相关。本研究的目的是检测miR-146a-5p和-193a-5p在CRC细胞周期进程中的作用。通过jetPEI转染试剂将miR-193a-5p和-146a-5p模拟物转染至HT-29 CRC细胞中,并评估它们对p53、细胞周期蛋白B和NF-κB基因表达的影响。通过流式细胞术评估这些微小RNA对细胞周期的抑制作用。通过蛋白质印迹法评估miR-193a-5p和miR-146a-5p对小鼠双微体2(MDM2)蛋白表达水平的影响。miR193a-5p和-146a-5p调节CRC细胞中MDM2蛋白的表达以及p53、细胞周期蛋白B和NF-κB基因的表达。用miRNA-146a-5p和-193a-5p处理HT-29细胞可诱导G1期细胞周期停滞。我们的研究结果表明,miR146a-5p和-193a-5p可能通过影响CRC细胞的细胞周期进程而作为潜在的肿瘤抑制因子。因此,在CRC患者的治疗中,恢复miRNA-146a-5p和-193a-5p的表达可能被推荐为一个潜在的治疗目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb1/6983996/f24ed241b627/apb-10-130-g001.jpg

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