Long noncoding RNA LINC01133 inhibits oral squamous cell carcinoma metastasis through a feedback regulation loop with GDF15.

BACKGROUND AND OBJECTIVES:Long noncoding RNAs (lncRNAs) play key roles in carcinoma metastasis. We aimed to investigate lncRNA LINC01133 in oral squamous cell carcinoma (OSCC) metastasis. METHODS:The RNA levels of LINC01133 and growth and differentiation factor 15 (GDF15) in tissue samples from OSCC patients, and OSCC cell lines were tested by real-time quantitative polymerase chain reaction (RT-qPCR). SPSS20.0 was used to perform statistical analysis of LINC01133 expression in clinical samples and correlate expression of LINC01133 and GDF15. Cell migration/invasion was assessed via transwell assays. Downstream genes of LINC01133 were screened using RNA-seq and validated by RT-qPCR. GDF15 protein levels were evaluated via Western blot analysis. RESULTS:LINC01133 was downregulated in OSCCs; higher expression of LINC01133 in OSCCs was correlated with less metastasis and better prognosis. LINC01133 inhibited OSCC cell migration and invasion. RNA-seq data showed that LINC01133 inhibited GDF15, and GDF15 could rescue inhibition of OSCC cell migration and invasion caused by LINC01133. Interestingly, GDF15 also inhibited LINC01133. Furthermore, a significant negative correlation between expression of LINC01133 and GDF15 was validated in the clinical study. CONCLUSIONS:Collectively, these data indicate that LINC01133 inhibited OSCC metastasis via a feedback regulation loop of reciprocal inhibition with GDF15, suggesting a new diagnostic and therapeutic target for OSCC.

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