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J Surg Oncol. 2018 Oct 17. doi: 10.1002/jso.25278. [Epub ahead of print]

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

Author information

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.

KEYWORDS:

LINC01133; feedback regulation loop; growth and differentiation factor 15 (GDF15); metastasis; oral squamous cell carcinoma (OSCC)

PMID:
30332510
DOI:
10.1002/jso.25278

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