Hypoxia Induced HMMR Promotes the NSCLC Progression

Abstract

\n Background: Hyaluronan mediated motility receptor (also known as RHAMM) is another one of few defined hyaluronan receptors, play pivotal roles in cell growth. However, the functionof HMMR in lung adenocarcinoma remain unclear.Methods: HMMR expression was analyzed emoloyed the public databases, the prognosis of HMMR was analysis by prognoscan, KMplot and GEPIA databases. The GO and KEGG pathway was analysis by the DAVID and GSEA software. The correlation between the HMMR expression was analysis by the TIMER databases, the gene and protein networks was analysis by Genemania and STRING databases, the DNA methylation was analysis by the MethSurv and UALCAN databases. The expression of HMMR was analysis by IHC and qPCR, the function of HMMR on cell proliferation and migration was examine by the cell growth curve, clone information, transwell and wound healing assay.Results: in this study, we find that HMMR was elevated in LUAD and it’s highly expression associated with the poor prognosis and lymph node metastasis. Furthermore, the expression of HMMR was induced by hypoxia in LUAD. HMMR expression level not only positively correlation with the different immune cells, but also positively correlation with the expression of immune checkpoints related gene. Finally, depletion of HMMR significantly represses the cell growth and migration of NSCLC. We also found that the HOXB7/TMPO-AS1/Let-7b-5p axis mediated high expression of HMMR in NSCLC, depletion of TMPO-AS1 and over-expression the Let-7b-5p would result in decreased the expression of HMMR in NSCLC cells, the TMPO-AS1 was positively with the HMMR and negatively related to the Let-7b-5p in NSCLC. Overall, this study emphasized the significance of HOXB7/TMPO-AS1/Let-7b-5p axis mediated high expression of HMMR in cancer progression and Immune infiltration of LUAD.Conclusions: we demonstrated HMMR was elevated in LUAD and positively relation to poor prognosis. We find the hypoxia microenvironment and DNA hypomethylation able to up-regulation of the HMMR expression. Additionally, HMMR expression was positive with the diverse immune cell and immune regulator related gene in LUAD. Finally, we found that depletion of HMMR was inhibits the cell proliferation and migration ability of NSCLC cells. These findings suggest that HMMR could be served as a biomarker for prognosis and immune infiltration in LUAD.