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.
Highlights
Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small-cell lung cancer [1, 2]
We aimed to explore the function and possible molecular mechanism of HMMR-AS1 involved in lung adenocarcinoma (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
Summary
Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small-cell lung cancer [1, 2]. LUAD has become one of the most common histological subtypes instead of squamous cell carcinoma in many countries [3]. There are various ways for treatment of LUAD, the mortality rate has not been significantly improved yet [4]. It’s critical to find novel therapeutic targets for improving the treatment. It has been reported that lncRNAs are involved in various significant cellular biological processes, including X-chromosome blots, stem cell differentiation, immune responses, cancer cell proliferation, as well as chemoresistance [6]. Recent reports have indicated that many lncRNAs, including PVT1, HOTAIR, LINC00673, ANRIL, HIT, and www.aging-us.com
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