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一种新型长链非编码 RNA 495810 通过稳定丙酮酸激酶同工酶 M2 促进结直肠癌的有氧糖酵解。

A novel lncRNA 495810 promotes the aerobic glycolysis in colorectal cancer by stabilizing pyruvate kinase isozyme M2.

机构信息

Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, Shanxi 030006, P.R. China.

College of Life Science, Shanxi University, Taiyuan, Shanxi 030006, P.R. China.

出版信息

Int J Oncol. 2023 May;62(5). doi: 10.3892/ijo.2023.5506. Epub 2023 Mar 24.

DOI:10.3892/ijo.2023.5506
PMID:36960860
Abstract

Aberrant expression of long non‑coding RNA (lncRNA) plays an important role in malignant progression of colon cancer and has become a new therapeutic target. In the present study, it was found that the expression of a novel lncRNA 495810 was significantly upregulated in colon cancer and correlated with poor prognosis in patients with colorectal cancer. The highly expressed lncRNA 495810 promoted the proliferation and inhibited apoptosis of CRC cells. Furthermore, the results of gene enrichment analysis indicated that 495810‑targeted genes were enriched in the glycolysis pathway and overexpression of 495810 enhanced aerobic glycolysis in colon cancer cells. More importantly, the expression of lncRNA 495810 was positively correlated with the glycolytic rate‑limiting enzyme pyruvate kinase isozyme M2 (PKM2). Notably, the data suggested that lncRNA 495810 physically interacted with PKM2 protein and enhanced PKM2 protein stability via the ubiquitin‑proteasome pathway. The present findings suggested that lncRNA 495810, a glycolysis‑related oncogenic lncRNA, is a potential biomarker for predicting prognosis and a therapeutic target for colon cancer.

摘要

长链非编码 RNA(lncRNA)的异常表达在结肠癌的恶性进展中起着重要作用,已成为新的治疗靶点。本研究发现,新型 lncRNA 495810 在结肠癌中表达显著上调,并与结直肠癌患者的不良预后相关。高表达的 lncRNA 495810 促进 CRC 细胞的增殖并抑制其凋亡。此外,基因富集分析的结果表明,495810 靶向基因富集在糖酵解途径中,并且 495810 的过表达增强了结肠癌细胞的有氧糖酵解。更重要的是,lncRNA 495810 的表达与糖酵解限速酶丙酮酸激酶同工酶 M2(PKM2)呈正相关。值得注意的是,数据表明 lncRNA 495810 与 PKM2 蛋白发生物理相互作用,并通过泛素-蛋白酶体途径增强 PKM2 蛋白稳定性。这些发现表明,lncRNA 495810 是一种与糖酵解相关的致癌 lncRNA,可作为预测预后的潜在生物标志物和结肠癌的治疗靶点。

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