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Background: Esophageal squamous cell carcinoma (ESCC) is a common malignant carcinoma of digestive system with high mortality. RAB, member RAS oncogene family like 6 (RABL6), a member of the RAS subfamily, has been reported as an important molecule in several cancers. However, its potential role in ESCC still remains unclear., Methods: RABL6 mRNA expression was detected in 93 frozen ESCC samples using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Immunohistochemistry was applied to evaluate the RABL6 expression in tissue microarray containing 171 pairs of ESCC tissues and paired para-cancerous tissues. We evaluated RABL6 expression and its correlation with clinicopathological characteristics and survival. Subsequently, the impact of RABL6 knockdown on the ability of cell proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT) of ESCC cells was investigated by MTS, Focus formation, flow cytometry, Transwell assays, qRT-PCR, western blot, inverted microscope observation and phalloidin staining, respectively., Results: Compared to paired para-cancerous tissues, RABL6 was highly expressed in ESCC. The RABL6 high-expression was associated with worse prognosis. We also revealed silencing of RABL6 caused inhibition of cell proliferation, invasion and migration. Further experiments demonstrated that knockdown of RABL6 suppressed the aggressive biological activities of ESCC by suppressing EMT in ESCC cells., Conclusions: RABL6 functions as a tumor oncogene in ESCC. It would be a potential biomarker predicting prognosis, and a novelty target for ESCC therapy.

Background: Esophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancer with high aggressiveness and poor prognosis. There is an urgent need for understanding the molecular mechanism underlying the development and progression of ESCC., Methods: ESCC tissues and corresponding non-neoplastic tissues were collected. The expression and function of miR-124-3p and BCAT1 in two cell lines KYSE-150 and Eca109 were determined., Results: We show downregulation of miR-124-3p expression in ESCC tissues, which is highly correlated with proliferation and migration of ESCC cell lines KYSE-150 and Eca109. miR-124-3p show high correlation with TNM stage and differentiation grade. Furthermore, miR-124-3p directly targets mRNA 3'UTR region of BCAT1, which results in upregulation of BCAT1 expression as observed in ESCC tissues and cell lines. Also, our data indicates that BCAT1 high expression is strongly linked to the disease-free survival, tumor size, pathologic stage, T classification and differentiation grade. On the other hand, we clarified the upstream mechanism regulating miR-124-3p expression in ESCC, which involves in the hypermethylation-silencing regulation mediated by DNA methyltransferase 1(DNMT1), which is of high expression in ESCC tissues and cell lines in the present study. In addition, DNMT1 knockdown or inhibition of DNMT1 function contributes to downregulation of miR-124-3p and BCAT1 expression., Conclusions: Our study thus clarifies a new mechanism that DNMT1/miR-124/BCAT1 axis regulates the development and progression of ESCC.