LncRNA TEX41 regulates autophagy by increasing Runx2 expression in lung adenocarcinoma bone metastasis

• Published in: American journal of translational research 2023-01, Vol.15 (2), p.949-966
• Main Authors: Li, Rong, Lin, Yanping, Hu, Fengdi, Liao, Yedan, Tang, Jiadai, Shen, Yan, Li, Heng, Guo, Jiangyan, Xie, Lin
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1943-8141; 1943-8141

To investigate the mechanism underlying the role of TEX41 in lung adenocarcinoma (LUAD) bone metastasis (BM). We analyzed the biological functions and molecular mechanisms of TEX41 using bioinformatics. TEX41 and Runx2 expressions were measured in clinical tissue samples and cell lines by quantitative PCR. The effects of TEX41 on LUAD cell proliferation, migration, invasion and metastasis as well as its mechanism of action were investigated. Fluorescence in-situ hybridization (FISH) was performed to determine TEX41 and Runx2 colocalization. Subcutaneous tumor growth and BM were evaluated in nude mice by X-ray and hematoxylin and eosin (HE) staining. TEX41 was dramatically increased in LUAD BM tissue, indicating a poorer prognosis in patients with LUAD and BM. TEX41 knockdown suppressed the migration and metastasis of LUAD cells, whereas TEX41 overexpression promoted these processes. Data from X-ray and HE staining showed that TEX41 supported the BM in LUAD. TEX41 overexpression induced autophagy in LUAD cells, as demonstrated by changes in autophagy markers. Results of FISH showed that TEX41 and Runx2 colocalized in the nucleus, and Runx2 expression was regulated by TEX41. The effects of TEX41 on LUAD cell migration, invasion, metastasis and autophagy were counteracted by Runx2 inhibition. Moreover, the role of TEX41 in the metastasis was partially dependent on autophagy, and phosphoinositide 3-kinase (PI3K)-AKT might be the major signaling pathway involved in TEX41-regulated autophagy. TEX41 promotes autophagy in LUAD cells by upregulating Runx2 to mediate LUAD migration, invasion and BM.