Wang C.-C.KANG-YI SUChen H.-Y.Chang S.-Y.Shen C.-F.Hsieh C.-H.Hong Q.-S.Chiang C.-C.Chang G.-C.SUNG-LIANG YUChen J.J.W.2020-06-302020-06-3020151932-6203https://scholars.lib.ntu.edu.tw/handle/123456789/507240Homeobox genes comprise a family of regulatory genes that contain a common homeobox domain and act as transcription factors. Recent studies indicate that homeobox A5 (HOXA5) may serve as a tumour suppressor gene in breast cancers. However, the precise role and the underlying mechanism of HOXA5 in lung cancer remain unclear. Oligonucleotide microarrays and an invasion/metastasis lung adenocarcinoma cell line model were used to determine the correlation between HOXA5 expression and cancer cell invasion ability. We found that ectopic expression of HOXA5 in highly invasive cancer cells suppressed cell migration, invasion, and filopodia formation in vitro and inhibited metastatic potential in vivo. Knockdown of HOXA5 promoted the invasiveness of lung cancer cells. In addition, HOXA5 expression was associated with better clinical outcome in non-small cell lung cancer patients with wild-type EGFR. Furthermore, genome-wide transcriptomic and pathway analyses were performed to identify the potential molecular mechanisms. Our data showed that HOXA5 may bind to the promoters of the cytoskeleton-related genes and downregulate their mRNA and protein expression levels. Our studies provide new insights into how HOXA5 may contribute to the suppression of metastasis in lung cancer via cytoskeleton remodelling regulation. Therefore, targeted induction of HOXA5 may represent a promising approach for non-small-cell lung cancer therapy. ? 2015 Wang et al.[SDGs]SDG3DNA; homeodomain protein; messenger RNA; protein HOXA5; unclassified drug; vasculotropin; EGFR protein, human; epidermal growth factor receptor; homeodomain protein; HOXA5 protein, human; protein binding; small interfering RNA; Article; cancer inhibition; cancer survival; cell invasion; cell migration; controlled study; disease association; DNA microarray; homeobox; HOXA5 gene; human; human cell; human tissue; in vitro study; in vivo study; lung cancer cell line; major clinical study; metastasis; non small cell lung cancer; oncogene; protein binding; protein expression; regulatory mechanism; animal; antagonists and inhibitors; cell motion; cell proliferation; cytoskeleton; disease free survival; disease model; fluorescence microscopy; genetics; lung tumor; metabolism; metastasis; mortality; mouse; non small cell lung cancer; pathology; promoter region; RNA interference; SCID mouse; survival rate; tumor cell line; xenograft; Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cytoskeleton; Disease Models, Animal; Disease-Free Survival; Homeodomain Proteins; Humans; Lung Neoplasms; Mice; Mice, SCID; Microscopy, Fluorescence; Neoplasm Metastasis; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Protein Binding; Receptor, Epidermal Growth Factor; RNA Interference; RNA, Small Interfering; Survival Rate; Transplantation, Heterologousjournal article10.1371/journal.pone.0124191258758242-s2.0-84929493511