Jianlu Kong1, Wenjie Sun2, Wenyuan Zhu3, Chuanxia Liu1, Honghe Zhang2, Huiming Wang1,3. 1. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, School of Medicine, Zhejiang University, Hangzhou, China. 2. Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China. 3. Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Abstract
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.
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.