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microR-1294-5p inhibits glycolytic metabolism of non-small cell lung cancer cells via targeting TMPRSS11B

JI ZHU#, XIYING BO#, GENGXI JIANG, SHIHUA YAO, TIEJUN ZHAO*, LING CHEN*

Department of Thoracic Surgery, Changhai Hospital of Shanghai, Shanghai, 200433, China

* Address correspondence to: Tiejun Zhao, email; Ling Chen, email
# These authors contributed equally to this work

BIOCELL 2021, 45(3), 639-647. https://doi.org/10.32604/biocell.2021.012847

Abstract

Non-small cell lung cancer (NSCLC) cells intake and consume glucose at high efficiency by aerobic glycolysis to maintain robust cell growth and resist cell death. MicroRNAs (miRNAs) have been known to play pivotal roles in NSCLC development partly through mediating glycolysis. However, only a few miRNAs have been experimentally confirmed as critical regulators of glycolysis in NSCLC. TCGA datasets were analyzed to screen for differentially expressed miRNAs between NSCLC and normal tissues. The function of miR-1294-5p was determined in NSCLC cells by cell proliferation, glucose uptake, lactate release, and Extracellular Acidification Rate (ECAR) assays. The target of miR- 1294-5p was predicted by TargetScan and miRDB, which was further validated by flow cytometry analysis, RT-qPCR, western blotting, a dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. In the present study, it was found that miR-1294-5p was a significantly downregulated miRNA in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The overexpression of miR-1294-5p inhibited glycolysis, lactate export, ECAR, and cell proliferation in NSCLC cells. Analysis with bioinformatic tools, Western Blotting, RT-qPCR, flow cytometry analysis, dual-luciferase reporter assay, and RIP assay showed that miR-1294-5p directly bound to complementary sites in the 3’-Untranslated Region (UTR) of TMPRSS11B resulted in downregulation of TMPRSS11B expression. In addition, transfection of recombinant TMPRSS11B rescued the functions of miR-1294-5p on glycolysis and proliferation of NSCLC cells. The findings provided novel insights for understanding the regulation of glycolytic metabolism in NSCLC.

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Cite This Article

ZHU, J., BO, X., JIANG, G., YAO, S., ZHAO, T. et al. (2021). microR-1294-5p inhibits glycolytic metabolism of non-small cell lung cancer cells via targeting TMPRSS11B. BIOCELL, 45(3), 639–647.



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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