miR‐942 promotes tumor migration, invasion, and angiogenesis by regulating EMT via BARX2 in non‐small‐cell lung cancer

• Published in: Journal of cellular physiology 2019-12, Vol.234 (12), p.23596-23607
• Main Authors: Yang, Fengming, Shao, Chuchu, Wei, Ke, Jing, Xinming, Qin, Zhiqiang, Shi, Yuenian, Shu, Yongqian, Shen, Hua
• Format: Article
• Language: English
• Subjects: A549 Cells; Animals; BARX2; Cadherins - biosynthesis; Carcinoma, Non-Small-Cell Lung - blood supply; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Movement - genetics; Epithelial-Mesenchymal Transition - genetics; epithelial–mesenchymal transition; Gene Expression Regulation, Neoplastic - genetics; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Human Umbilical Vein Endothelial Cells; Humans; Lung Neoplasms - blood supply; Lung Neoplasms - genetics; Lung Neoplasms - pathology; metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; miR‐942; Neoplasm Invasiveness - genetics; Neoplasm Metastasis - genetics; Neoplasm Transplantation; Neovascularization, Pathologic - genetics; NSCLC; Transplantation, Heterologous; Vimentin - biosynthesis
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28928

Epithelial–mesenchymal transition (EMT) has an important function in cancer. Recently, microRNAs have been reported to be involved in EMT by regulating target genes. miR‐942 is considered a novel oncogene in esophageal squamous cell carcinoma. However, its role in non‐small‐cell lung cancer (NSCLC) has not been investigated. In this study, the expression of miR‐942 in NSCLC patients tumor and paired adjacent tissues were assessed by quantitative real‐time polymerase chain reaction and in situ hybridization. Transwell, wound healing, tube formation, and tail vein xenograft assays were conducted to assess miR‐942′s function in NSCLC. Potential miR‐942 targets were confirmed using dual‐luciferase reporter assays, immunohistochemistry, immunoblot, and rescue experiments. The results showed miR‐942 is relatively highly expressed in human NSCLC tissues and cells. In vitro assays demonstrated that overexpression of miR‐942 promoted cell migration, invasion, and angiogenesis. Tail vein xenograft assays suggested that miR‐942 contributed to NSCLC metastasis in vivo. Three bioinformatics software was searched, and BARX2 was predicted as a downstream target of miR‐942. Direct interaction between them was validated by dual‐luciferase assays. Rescue experiments further confirmed that BARX2 overexpression could reverse functional changes caused by miR‐942. Moreover, miR‐942 increased EMT‐associated proteins N‐cadherin and vimentin by inhibiting BARX2, while E‐cadherin expression is reduced. In summary, this study reveals that miR‐942 induces EMT‐related metastasis by directly targeting BARX2, which may provide a potential therapeutic strategy for NSCLC. IVIS Lumina II system was used to detect lung metastatic nodule of nude mice. The result showed miR‐942 promotes non‐small‐cell lung cancer metastasis in vivo.