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

ABSTRACT:

Purpose

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).

Experimental design

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 in vitro experimental findings.

Results

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 in vitro 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 in vivo.

Conclusions

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.

SUBMITTER: Cai Y 

PROVIDER: S-EPMC6555459 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature