LncRNA HMMR-AS1 promotes proliferation and metastasis of lung adenocarcinoma by regulating MiR-138/sirt6 axis
Autor: | Jiying Wang, Yun Chen, Zhaoying Sheng, Yong Cai |
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Rok vydání: | 2019 |
Předmět: |
SIRT6
sirt6 Aging Lung Neoplasms proliferation miR-138 Adenocarcinoma Biology medicine.disease_cause Metastasis medicine Humans Sirtuins Extracellular Matrix Proteins Gene knockdown Competing endogenous RNA Cell growth HMMR-AS1 apoptosis Cell Biology medicine.disease MicroRNAs tumorigenesis Hyaluronan Receptors A549 Cells Case-Control Studies lung adenocarcinoma (LUAD) Cancer research RNA Long Noncoding Carcinogenesis Research Paper |
Zdroj: | Aging (Albany NY) |
ISSN: | 1945-4589 |
DOI: | 10.18632/aging.101958 |
Popis: | 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. |
Databáze: | OpenAIRE |
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