Overexpression Of Long Noncoding RNA HMMR-AS1 Promotes Progression In Lung Adenocarcinoma

Objective: Long non-coding RNA(Lnc RNA)is a class of non-coding RNA with a length larger than 200 nucleotides,and the mechanism of its abnormal expression affecting the malignant progression of tumors has become a hot topic for many scholars.As a novel lnc RNA,the role of lnc RNA HMMR-AS1 in lung adenocarcinoma(LUAD)is still unclear.Here,we investigated the HMMR-AS1 expression in LUAD and explored the effect of HMMR-AS1 on the phenotype of lung adenocarcinoma cells in vitro and its prognosis,to provide a therapeutic target for LUAD treatment targeted therapy.Methods: 1.The gene expression profiles of GSE19188 including 65 normal lung epithelial tissues and 45 lung adenocarcinoma tissues were downloaded from the Gene Expression Omnibus(GEO)database(http://www.ncbi.nlm.nil.gov/geo/).Differentially expressed lnc RNAs were screened by a series of bioinformatics analysis.2.The human normal lung epithelial cell line BEAS-2A and human LUAD cell lines A549 and H1299 were purchased from Shanghai Institute of Cell Biology.The level of HMMR-AS1 and its sense transcript HMMR were verified by real-time fluorescence quantitative polymerase chain reaction(RT-q PCR).3.Si-HMMR-AS1 was transfected into A549 and H1299 cells,and the transfection efficiency was detected by RT-q PCR.Also,RT-q PCR and western blot were used to evaluate the expression of HMMR in m RNA and protein level after transfection with si-HMMR-AS1.4.CCK-8,Clone formation,flow cytometric analysis,wound scratch assay and transwell assay were used to assess the biological function of A549 and H1299 cells.5.Kaplan-Meier plotter database was used to evaluate the prognostic value of HMMR-AS1 and HMMR in LUAD patients.Results: 1.Through reanalyzing the LUAD RNA sequencing data in GEO dataset GSE19188,a total of 81 differentially expressed lnc RNAs were identified in LUAD tissues compared with normal lung epithelial tissues.Further analysis revealed that the level of HMMR-AS1 in LUAD was significantly increased 2.08 folds(t = 14.1,P < 0.01).The expression of the sense strand HMMR was also increased 2.37 folds(t = 13.04,P < 0.01).2.Compared to the human normal lung epithelial cell line BEAS-2A,HMMR-AS1 expression was upregulated 3.06 and 5.02 folds respectively in A549 and H1299 cells.3.After transfection with si-HMMR-AS1,the expression of HMMR-AS1 in A549 and H1299 cells was significantly decreased(P<0.05),and the expression of HMMR markedly reduced in transcription and protein levels(P<0.05).4.The phenotypic experiment results showed that knockdown of HMMR-AS1 significantly inhibited the proliferation and migration abilities and increased the apoptosis rates of A549 and H1299 cells compared with the negative control group.5.Kaplan-Meier Plotter database analysis showed that patients with high expression of HMMR-AS1 and HMMR had a poor prognosis compared with patients with low expression(P < 0.05).Conclusion : Lnc RNA HMMR-AS1 is overexpression in LUAD,which could promote the growth,migration and invasion of LUAD cells and was associated with poor prognosis,suggesting that HMMR-AS1 might be a potential target for LUAD treatment.