Long non-coding RNA MIR155HG knockdown suppresses cell proliferation, migration and invasion in NSCLC by upregulating TP53INP1 directly targeted by miR-155-3p and miR-155-5p

X.-Y. Ren, Y.-D. Han, Q. Lin

Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. xklinqiang@hotmail.com

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• Oncology

OBJECTIVE: Previous studies have proved that lncRNA MIR155 host gene (MIR155HG) is overexpressed in glioma and has elucidated its function. However, its functional role and underlying molecular mechanism in non-small cell lung cancer (NSCLC) are unknown. This study aimed to investigate the function and underlying mechanism of MIR155HG in NSCLC.

MATERIALS AND METHODS: Differentially expressed lncRNAs in NSCLC tissue were identified from Gene Expression Omnibus (GEO) database. The expression of MIR155HG, miR-155-3p, miRNA-155-5p, and tumor protein p53-inducible nuclear protein 1 (TP53INP1) in NSCLC specimens and cells were quantified using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell invasion assay were performed to evaluate cell viability and the ability of migration and invasion. Luciferase reporter assay was employed to examine whether miR-155-3p and miR-155-5p could bind to TP53INP1 in NSCLC cells. A xenograft tumor model was used to evaluate the biological function of MIR155HG in vivo.

RESULTS: Data obtained from the GEO dataset show that MIR155HG is frequently overexpressed in NSCLC tumor tissues and cell lines. Elevated MIR155HG levels were found to be associated with advanced disease stage and poor prognosis of NSCLC. Cell viability, as well as the capability of migration and invasion of NCI-H1975 and A549 cells, was markedly reduced upon MIR155HG knockdown. Mechanistically, bioinformatics analysis and functional assays confirmed that miR-155-5p and miR-155-3p, two derivatives of MIR155HG, contributed to the effect of MIR155HG in NSCLC. It was also found that miR-155-5p or miR-155-3p mimics could dramatically rescue the inhibition of cell proliferation, migration, and invasion caused by siMIR155HG. Furthermore, bioinformatics analysis and Luciferase reporter assays revealed that miR-155-5p and miR-155-3p mediate the effect of MIR155HG in NSCLC cells by negatively regulating the tumor suppressor TP53INP1.

CONCLUSIONS: Current findings indicate that MIR155HG/miR-155 axis facilitates NSCLC progression by downregulating TP53INP1. Therefore, the MIR155HG/miR-155 axis may be a potential therapeutic target for NSCLC.

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