Long non‐coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA‐125b/STAT3 axis

• Published in: Journal of cellular physiology Vol. 233; no. 4; pp. 3384 - 3396
• Main Authors: Chang, Shi‐Min, Hu, Wei‐Wei
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2018
• Subjects: Adenocarcinoma; Adenocarcinoma of Lung - genetics; Animal models; Apoptosis - genetics; Bioinformatics; Cell Line, Tumor; Cell Proliferation - genetics; Epithelial Cells - metabolism; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Humans; In vivo methods and tests; Lung cancer; Lungs; MALAT1; Metastases; Metastasis; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐125b; Non-coding RNA; Oral cancer; Oral squamous cell carcinoma; OSCC; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Squamous cell carcinoma; STAT3; Stat3 protein; STAT3 Transcription Factor - metabolism; Studies; Transcription; Tumors; OSCC; miR-125b; MALAT1; STAT3
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26185

Oral squamous cell carcinoma (OSCC), as the most common type of oral cancer, is responsible for almost 3% of all malignant tumors worldwide. Non‐coding RNAs such as lncRNAs and microRNAs have been involved in many cancers including OSCC. Recently, lncRNA metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) has been reported to play an oncogenic role in OSCC metastasis. However, the underlying mechanism of MALAT1 in regulating OSCC progression remains unclear. The aim of this study was to investigate the specific role of MALAT1 in OSCC development. It was observed that MALAT1 was upregulated in OSCC cell lines. Inhibition of MALAT1 can prevent OSCC proliferation while overexpressing MALAT1 promoted OSCC progression. In addition, bioinformatics search was used to identify that miR‐125b was a direct target of MALAT1, which indicated a negative correlation between MALAT1 and miR‐125b. Besides these, STAT3 was predicted as a binding target of miR‐125b in OSCC. Overexpression of MALAT1 was able to suppress the tumor inhibitory effect of miR‐125b mimics via upregulating STAT3. Moreover, the function of MALAT1 in OSCC development was further investigated by using in vivo assays. The established nude mice models revealed that downregulated MALAT1 greatly inhibited OSCC tumor growth and reversely upregualated MALAT1 promoted OSCC development via miR‐125b/STAT3 axis, respectively. In conclusion, MALAT1 can function as a competing endogenous RNA (ceRNA) to modulate STAT3 expression by absorbing miR‐125b in OSCC and could be used as a novel therapeutic target in OSCC diagnosis and treatment. Our findings in OSCC cell lines and xenografts suggested MALAT1 as an oncogene, which can promote OSCC development. This was the first report to demonstrate that MALAT1 can function as a ceRNA and modulate STAT3 expression by sponging miR‐125b in OSCC both in vitro and in vivo. Our data indicated that MALAT1 could be used as a therapeutic target in OSCC diagnosis and treatment.