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lncRNA PVT1的敲低通过miR-761/MAPK1轴抑制结肠癌细胞的增殖并加速其凋亡。

Knockdown of lncRNA PVT1 inhibits the proliferation and accelerates the apoptosis of colorectal cancer cells via the miR‑761/MAPK1 axis.

作者信息

Liu Yujing, Wu Yongyou, Zhu Zhu, Gong Jiangbo, Dou Wenhuan

机构信息

Department of General Surgery, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China.

Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.

出版信息

Mol Med Rep. 2021 Nov;24(5). doi: 10.3892/mmr.2021.12434. Epub 2021 Sep 13.

Abstract

Colorectal cancer (CRC) is associated with high morbidity rates. Long non‑coding RNAs (lncRNAs) participate in the development of CRC. However, the potential roles of lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC remain unknown. Therefore, the aim of the present study was to investigate the potential roles of PVT1 in CRC. Reverse transcription‑quantitative PCR and western blot analyses were conducted to determine the mRNA and protein expression levels. The cellular behaviors were detected using 5‑Ethynyl‑2'‑deoxyuridine, Cell Counting Kit‑8 and flow cytometry assays. The interaction between PVT1 and microRNA (miR)‑761 or MAPK1 was confirmed using a dual‑luciferase reporter assay. Moreover, the Pearson's method was applied for correlation analysis. The results demonstrated that the expression levels of PVT1 and MAPK1 were upregulated, while miR‑761 was downregulated in CRC tissues. The expression of PVT1 was positively correlated with MAPK1 and negatively correlated with miR‑761. In addition, PVT1 sponged miR‑761 to upregulate MAPK1 expression. It was found that the knockdown of PVT1 expression inhibited the proliferation and promoted the apoptosis of CRC cells, which was more potent in cells transfected with miR‑761. The regulatory role of small interfering RNA‑PVT1 on the expression of apoptosis‑related genes was reduced by MAPK1. Collectively, the present results suggested that knockdown of PVT1 may inhibit the progression of CRC by regulating the miR‑761/MAPK1 axis, which may provide a promising biomarker for the treatment of CRC.

摘要

结直肠癌(CRC)的发病率很高。长链非编码RNA(lncRNA)参与了结直肠癌的发生发展。然而,lncRNA浆细胞瘤变异易位1(PVT1)在结直肠癌中的潜在作用尚不清楚。因此,本研究的目的是探讨PVT1在结直肠癌中的潜在作用。进行逆转录定量PCR和蛋白质印迹分析以确定mRNA和蛋白质表达水平。使用5-乙炔基-2'-脱氧尿苷、细胞计数试剂盒-8和流式细胞术检测细胞行为。使用双荧光素酶报告基因检测法确认PVT1与微小RNA(miR)-761或丝裂原活化蛋白激酶1(MAPK1)之间的相互作用。此外,采用Pearson方法进行相关性分析。结果表明,在结直肠癌组织中,PVT1和MAPK1的表达水平上调,而miR-761的表达水平下调。PVT1的表达与MAPK1呈正相关,与miR-761呈负相关。此外,PVT1通过海绵吸附miR-761来上调MAPK1的表达。发现敲低PVT1表达可抑制结直肠癌细胞的增殖并促进其凋亡,这在转染miR-761的细胞中更为明显。小干扰RNA-PVT1对凋亡相关基因表达的调节作用被MAPK1减弱。总的来说,目前的结果表明,敲低PVT1可能通过调节miR-761/MAPK1轴来抑制结直肠癌的进展,这可能为结直肠癌的治疗提供一个有前景的生物标志物。

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