LncRNA HMMR-AS1 promotes proliferation and metastasis of lung adenocarcinoma by regulating MiR-138/sirt6 axis

• Published in: Aging (Albany, NY.) Vol. 11; no. 10; pp. 3041 - 3054
• Main Authors: Cai, Yong, Sheng, Zhaoying, Chen, Yun, Wang, Jiying
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 25.05.2019
• Subjects: Research Paper; miR-138; lung adenocarcinoma (LUAD); proliferation; sirt6; apoptosis; tumorigenesis; HMMR-AS1
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.101958

Long noncoding RNAs (lncRNA) play critical roles in cancer development. In this study, we aimed to explore the function and possible molecular mechanism of HMMR-AS1 involved in lung adenocarcinoma (LUAD). Firstly, we analyzed HMMR-AS1 expression in LUAD tissues with the sequencing data from The Cancer Genome Atlas (TCGA). Next, we evaluated the effects of HMMR-AS1 on LUAD cell proliferation and apoptosis, and its regulation of miR-138 by acting as a ceRNA. The animal model was used to support the experimental findings. HMMR-AS1 expression was significantly upregulated in LUAD tissues and was associated with larger tumor diameter, advanced TNM stage, lymph node metastasis, and shorter survival. Knockdown of HMMR-AS1 induced apoptosis and growth arrest and inhibited tumorigenesis in mouse xenografts. Mechanistically, HMMR-AS1 functioned as a ceRNA of miR-138, thereby leading to repression of its endogenous target sirt6. Moreover, knockdown of HMMR-AS1 dramatically inhibited tumor growth and metastasis of LUAD . Taken together, HMMR-AS1 is significantly over-expressed in LUAD, and HMMR-AS1-miR-138-sirt6 axis play a critical role in LUAD tumorigenesis. Our findings highlight an oncogenic role of HMMR-AS1 in LUAD.