lncRNA OXCT1-AS1 Promotes Metastasis in Non-Small-Cell Lung Cancer by Stabilizing LEF1, In Vitro and In Vivo.

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the metastasis of non-small-cell lung cancer (NSCLC). This study is aimed at investigating the biological role of lncRNA OXCT1-AS1 in NSCLC metastasis and the underlying regulatory mechanisms. The expression profiles of lncRNA OXCT1-AS1 in different NSCLC cell lines were examined. Then, the ...
biological function of lncRNA OXCT1-AS1 in NSCLC metastasis was explored by loss-of-function assays in vitro and in vivo. Further, the protective effect of lncRNA OXCT1-AS1 on lymphoid enhancer factor 1 (LEF1) was examined using RNA pull-down and RNA immunoprecipitation assays. Additionally, the role of LEF1 in NSCLC metastasis was investigated. Results indicated that lncRNA OXCT1-AS1 expression was significantly increased in NSCLC cell lines. Functional analysis revealed that knockdown of lncRNA OXCT1-AS1 impaired invasion and migration in vitro. Additionally, the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis was also confirmed in vivo. Mechanistically, through direct interaction, lncRNA OXCT1-AS1 maintained LEF1 stability by blocking NARF-mediated ubiquitination. Furthermore, LEF1 knockdown impaired invasion and migration of NSCLC in vitro and in vivo. Collectively, these data highlight the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis by stabilizing LEF1 and suggest that lncRNA OXCT1-AS1 represents a novel therapeutic target in NSCLC.
Mesh Terms:
Amino Acid Sequence, Animals, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Cell Movement, Female, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms, Male, Mice, Nude, Models, Biological, Neoplasm Invasiveness, Neoplasm Metastasis, Protein Stability, RNA, Long Noncoding, TCF Transcription Factors, Ubiquitination, Up-Regulation
Biomed Res Int
Date: Aug. 03, 2021
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