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下调微小RNA-144通过调节葡萄糖转运蛋白1(GLUT1)的表达介导肺癌细胞的代谢转变。

Downregulating microRNA-144 mediates a metabolic shift in lung cancer cells by regulating GLUT1 expression.

作者信息

Liu Min, Gao Jun, Huang Qin, Jin Yanfeng, Wei Zhonghua

机构信息

Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.

出版信息

Oncol Lett. 2016 Jun;11(6):3772-3776. doi: 10.3892/ol.2016.4468. Epub 2016 Apr 19.

Abstract

Lung cancer is the leading cause of cancer-associated mortality worldwide. Increasing evidence has found that cancer metabolism alternations represent a critical hallmark for lung cancer. There is an urgent requirement to understand and dissect the molecular mechanisms underlying cancer metabolism for lung cancer therapy. It remains largely unknown whether the deregulation of miRNAs contributes to the cancer metabolism. The present study aimed to investigate the role of miR-144 in lung cancer. Glucose uptake rate and lactate production assays demonstrated that miR-144 expression is decreased and therefore enhances the aerobic metabolism in lung cancer cells. In addition, western blot analysis revealed that miR-144 performs this function by increasing the expression of glucose transporter 1 (GLUT1), leading to an increase in glucose uptake and lactate production. Furthermore, cell viability assays demonstrated that the altered metabolism induced by miR-144 results in the rapid growth of cancer cells. In conclusion, these results identify miR-144 as a molecular switch involved in the orchestration of the Warburg effect in lung cancer cells via targeting the expression of GLUT1.

摘要

肺癌是全球癌症相关死亡的主要原因。越来越多的证据表明,癌症代谢改变是肺癌的一个关键标志。迫切需要了解和剖析肺癌治疗中癌症代谢背后的分子机制。miRNA的失调是否促成癌症代谢在很大程度上仍然未知。本研究旨在探讨miR-144在肺癌中的作用。葡萄糖摄取率和乳酸生成测定表明,miR-144表达降低,从而增强肺癌细胞的有氧代谢。此外,蛋白质印迹分析显示,miR-144通过增加葡萄糖转运蛋白1(GLUT1)的表达来发挥这一功能,导致葡萄糖摄取和乳酸生成增加。此外,细胞活力测定表明,miR-144诱导的代谢改变导致癌细胞快速生长。总之,这些结果确定miR-144是一种分子开关,通过靶向GLUT1的表达参与肺癌细胞中瓦伯格效应的调控。

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