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

• Published in: BioMed research international 2021, Vol.2021 (1), p.4959381-4959381
• Main Authors: Li, Binru, Zhu, Libo, Li, Linlin, Ma, Rui
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Bioengineering; Biotechnology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Complications and side effects; Development and progression; Female; Functional analysis; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Humans; Immunoprecipitation; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lymphatic system; Male; Medical prognosis; Metastases; Metastasis; Mice; Mice, Nude; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis; Non-small cell lung carcinoma; Physiological aspects; Plasmids; Protein Stability; Proteins; Reagents; Regulatory mechanisms (biology); Risk factors; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Small cell lung carcinoma; TCF Transcription Factors - chemistry; TCF Transcription Factors - metabolism; Therapeutic targets; Transcription factors; Ubiquitination; Up-Regulation - genetics
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2021/4959381

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.