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Exp Cell Res. 2018 Jan 1;362(1):90-101. doi: 10.1016/j.yexcr.2017.11.006. Epub 2017 Nov 8.

Up-regulated miR-548k promotes esophageal squamous cell carcinoma progression via targeting long noncoding RNA-LET.

Author information

1
Department of Surgical Oncology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China.
2
Department of Surgical Oncology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China. Electronic address: huangzj@fjmu.edu.cn.

Abstract

Dysregulated noncoding RNAs have been observed in diverse cancers. MIR458K is frequently amplified in esophageal squamous cell carcinoma (ESCC). However, the expression, clinical significances, and action mechanisms of miR-548k in ESCC are still unclear. In this study, we found that miR-548k is significantly up-regulated in ESCC tissues and cell lines. Up-regulated miR-548k expression is significantly correlated with advanced invasion depth, lymph node metastasis, advanced TNM stage, and poor overall survival. Gain-of- and loss-of-function assays demonstrated that miR-548k promotes the proliferation and migration of ESCC cells in vitro and tumor growth in vivo. Mechanistically, we found that miR-548k directly targets and represses the expression of long noncoding RNA-LET (lncRNA-LET), and further down-regulates p53 and up-regulates NF90. In addition, we found that lncRNA-LET is down-regulated and inversely correlated with miR-548k in ESCC. Down-regulated lncRNA-LET also indicated poor overall survival of ESCC patients. Functional assays demonstrated that lncRNA-LET inhibits the proliferation and migration of ESCC cells, and the effects of miR-548k on ESCC are dependent on the negative regulation of lncRNA-LET. In summary, our data revealed the critical roles of miR-548k-lncRNA-LET regulation axis in ESCC and suggested that the miR-548k-lncRNA-LET regulation axis may be promising prognostic biomarkers and therapeutic targets for ESCC.

KEYWORDS:

Esophageal squamous cell carcinoma; LncRNA-LET; Long noncoding RNA; MiR-548k; Migration; Proliferation

PMID:
29126868
DOI:
10.1016/j.yexcr.2017.11.006
[Indexed for MEDLINE]

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