NKX2-1-AS1 promotes the lymphangiogenesis of lung adenocarcinoma through regulation of ERG-mediated FABP4

• Published in: Tissue & cell Vol. 87; p. 102314
• Main Authors: Tao, Ting, Chen, Hui, Xu, Qimei, Li, Zhen, Chen, Xuelian, Zhou, Xunjian, Luo, Wu
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.04.2024
• Subjects: Adenocarcinoma - genetics; Cell Line, Tumor; Cell Proliferation - genetics; ERG; FABP4; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - metabolism; Gene Expression Regulation, Neoplastic; Humans; Lung - pathology; Lung adenocarcinoma; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lymphangiogenesis; Lymphangiogenesis - genetics; MicroRNAs - genetics; NKX2–1-AS1; RNA, Long Noncoding - genetics; Transcriptional Regulator ERG - genetics; Transcriptional Regulator ERG - metabolism; VEGF-C; VEGF-C; FABP4; ERG; Lung adenocarcinoma; NKX2–1-AS1; Lymphangiogenesis
• ISSN: 0040-8166; 1532-3072
• DOI: 10.1016/j.tice.2024.102314

Lymphatic metastasis is a common metastasis of lung adenocarcinoma (LUAD). The current study illustrated the action of lncRNA NKX2–1-AS1 in lymphangiogenesis in LUAD and the underlying mechanisms. Clinical tissue samples were collected for determining NKX2–1-AS1 expression. Then, H441 and H661 cells were selected to perform gain- and loss-of-function assays for dissecting the roles of NKX2–1-AS1 in LUAD cell proliferation and migration. Besides, H441 and H661 cell supernatant was harvested to stimulate HLECs for assessing tube formation ability. Interaction among NKX2–1-AS1, ERG, and fatty acid binding protein 4 (FABP4) was validated through luciferase and RIP assays. NKX2–1-AS1 was highly-expressed in LUAD tissues. Silencing NKX2–1-AS1 suppressed H441 and H661 cell proliferation and migration, reduced expression levels of lymphangiogenesis-related factors (LYVE-1, VEGF-C, VEGFR3, VEGF-A, VEGFR2, and CCR7), and inhibited HLEC tube formation. Interaction validation demonstrated that NKX2–1-AS1 regulated FABP4 transcription by binding to ERG. Overexpression of FABP4 could effectively block the inhibition role of NKX2–1-AS1 silencing in lymphangiogenesis in H441 and H661 cells. This study provided evidence that NKX2–1-AS1 regulated FABP4 transcription by binding to ERG to facilitate the proliferation and migration of LUAD cells and tube formation of HLECs, thus participating in lymphangiogenesis. •NKX2-1-AS1 is highly expressed in LUAD.•Silencing NKX2-1-AS1 inhibits lymphangiogenesis in LUAD cells.•NKX2-1-AS1 binds to transcription factor ERG to regulate the expression of FABP4.•NKX2-1-AS1 promotes lymphangiogenesis in LUAD cells through regulation of FABP4.•This study provides a new therapeutic target for lymphangiogenesis in LUAD.