MicroRNA-181d is a tumor suppressor in human esophageal squamous cell carcinoma inversely regulating Derlin-1

Abstract

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of human esophageal cancer in East Asia. In the present study, we explored the tumor suppressive function of microRNA-181d (miR-181d) in ESCC. Quantitative RT-PCR was used to assess gene levels of MIR-181d in both ESCC cell lines and clinical samples. Lentiviral transduction was used to overexpress MIR-181d in ECA109 and Kyse30 cells. The possible tumor suppressive effects of MIR-181d overexpression on ESCC proliferation, migration and cell cycle transition in vitro, and tumorigenicity in vivo were examined. Downstream target gene of MIR-181d in ESCC, Derlin-1 (DERL1) was assessed by luciferase assay and qRT-PCR. DERL1 was also force expressed in MIR-181d-overexperssed ECA109 and Kyse30 cells to evaluate its reverse effect on MIR-181d mediated tumor suppression in ESCC. MIR-181d was aberrantly downregulated in both ESCC cell lines and human tumors. Lentivirus-mediated MIR-181d overexpression had significant tumor suppressing functions by inhibiting cancer proliferation, migration and arresting cell cycle transition in vitro, as well as inhibiting tumorigenicity in vivo. DERL1 was identified as downstream target gene of MIR-181d in ESCC cells. Forced overexpression of DERL1 in ESCC cells was shown to greatly reverse the tumor suppressive effects of MIR-181d upregulation on ESCC in vitro proliferation, migration and cell cycle arrest. Out data suggest that MIR-181d is a tumor suppressor in ESCC inversely regulating its downstream target gene of DERL1.