Abstract
Long non-coding RNAs (lncRNAs) have been involved in the process of cancer occurrence, progression, and treatment. Lung cancer-related lncRNAs are still an emerging field, thus we sought to identify novel functional lncRNAs as candidate targets in lung cancer. Here, we identified one novel lncRNA, MUC5B-AS1 (Ensembl: ENST00000532061.2). MUC5B-AS1 was upregulated in lung adenocarcinoma tissues compared with normal lung tissues. Moreover, MUC5B-AS1 promoted lung cancer cell migration and invasion in vitro and promoted lung cancer cell metastasis in vivo. MUC5B-AS1 and its cognate sense transcript MUC5B were highly co-expressed and mutually regulated in lung adenocarcinoma. Mechanistically, MUC5B-AS1 promoted cell migration and invasion by forming an RNA–RNA duplex with MUC5B, thereby increasing MUC5B expression levels in lung adenocarcinoma. The high expression of MUC5B was significantly associated with poor outcomes in lung adenocarcinoma. Our findings highlight MUC5B-AS1 functions as an oncogenic lncRNA in tumor metastasis and implicate MUC5B-AS1 as an attractive candidate target for lung adenocarcinoma treatment.
Highlights
Lung cancer continues to be the most common malignancies and the leading cause of cancer mortality worldwide[1,2]
In order to confirm the non-coding nature of MUC5B-AS1, coding-potential analysis was performed by Coding Potential Assessment Tool (CPAT)[23] and Coding Potential Calculator (CPC) computational algorithm[24], which predicted that MUC5B-AS1 had a very low coding potential (Fig. 1b)
In this study, we demonstrated that MUC5B-AS1, a new long non-coding antisense transcript for MUC5B, was significantly upregulated in lung adenocarcinoma tissues
Summary
Lung cancer continues to be the most common malignancies and the leading cause of cancer mortality worldwide[1,2]. Adenocarcinoma is the major subtype of lung cancer[3]. The discovery of oncogenes and tumor suppressor genes leads to profound insights into the mechanisms of lung cancer, the overall 5-year survival rate is less than 20%3. The poor prognosis of lung cancer is largely due to early metastasis[4]. Identification of novel therapeutic targets for invasion and metastasis may provide alternative approaches for management of patients with lung cancer. Accumulating evidences have suggested that majority of lncRNAs are likely to regulate the targeted gene transcription[6], and function in post-transcriptional[7] and epigenetic regulation of genes[8]
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