Open Access
ARTICLE
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, ; Ling Chen,
# These authors contributed equally to this work
BIOCELL 2021, 45(3), 639-647. https://doi.org/10.32604/biocell.2021.012847
Received 14 July 2020; Accepted 14 September 2020; Issue published 03 March 2021
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.
Keywords
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.