Silencing of LINC00461 enhances radiosensitivity of lung adenocarcinoma cells by down-regulating HOXA10 via microRNA-195.

Lung adenocarcinoma is recognized as one of the most recurrent tumours in adults. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts and have been demonstrated to regulate biological functions during tumorigenesis. Our study aims to investigate the underlying molecular mechanisms of LINC00461/microRNA-195 (miR-195)/HOXA10 responsible for its involvement in lung adenocarcinoma. We firstly selected differentially expressed lncRNAs and genes by the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO). The functional role of LINC00461 in lung adenocarcinoma was then determined using ectopic expression, knockdown and reporter assay experiments. Besides, we detected the expression profiles of LINC00461, miR-195, HOXA10 and apoptosis- and invasion-related genes. Cell proliferation, migration and invasion were evaluated. In vivo tumour formation ability was analysed. Overexpressed LINC00461 and HOXA10 but down-regulated miR-195 were observed in primary and metastatic lung adenocarcinoma. LINC00461 negatively regulated miR-195, while miR-195 negatively regulated HOXA10. Forced LINC00461 expression decreased expression of miR-195 and Bax, increased expression of HOXA10, MMP-2, MMP-9 and Bcl-2, promoted cell proliferation, migration and invasion as well as tumour formation, and enhanced radiosensitivity of lung adenocarcinoma cells. However, these effects were reversed by lentivirus-mediated miR-195-forced expression, thereby suggesting that miR-195 could antagonize the harmful effect of LINC00461 on lung adenocarcinoma cells. Collectively, the present study provides evidence supporting the inhibitory effect of LINC00461 silencing on lung adenocarcinoma, which suppresses lung adenocarcinoma cell migration, invasion and radiosensitivity via HOXA10 by binding to miR-195, which provides a promising basis for the targeted intervention treatment for human lung adenocarcinoma.