MiR-212-3p mediates apoptosis and invasion of esophageal squamous cell carcinoma through inhibition of the Wnt/β-catenin signaling pathway by targeting SOX4

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in East Asia, with approximately half of ESCC cases occurring in China. ESCC poses a serious threat to the quality of life of patients. MicroRNAs (miRNAs) are extremely important in the occurrence and development of ESCC. Current studies have shown that miR-212-3p is expressed at low levels in esophageal adenocarcinoma tumor tissues; however, its function and mechanism in ESCC have not been studied. Methods:The expression levels of miR-212-3p and SOX4 were detected by quantitative polymerase chain reaction (qPCR) in ESCC tissues and adjacent tissues, and ESCC cell lines from 60 patients. The interaction of miR-212-3p and SOX4 was determined using a dual-luciferase reporter gene system. EC9706 Cells were transfected with miR-212-3p mimic, NC mimic, si-NC and si-SOX4 and miR-212-3p mimic + overexpressing-SOX4, and the effects on miR-212-3p and SOX4 expression were observed, respectively. An MTT assay was carried out to detect the proliferation ability of ESCC. The invasion ability and apoptosis level of the cells were determined by Transwell assay and flow cytometry, respectively. qPCR was used to detect expression of miR-212-3p and SOX4. Western blot was performed to observe the expression of SOX4, Wnt1, β-catenin, c-Myc, and Cyclin D1.Results: miR-212-3P was observed to be down-regulated in ESCC tissues and cells, while SOX4 expression was up-regulated; the two were negatively correlated. The dual-luciferase reporter gene further confirmed that miR-212-3p targeted SOX4. miR-212-3p overexpression and interference with SOX4 significantly inhibited the proliferation and invasion of ESCC EC970 cells, and promoted apoptosis.Furthermore, the results of Western blot confirmed that miR-212-3p overexpression and interference with SOX4 down-regulated the expression of Wnt1, β-catenin, c-Myc, and Cyclin D1. Meanwhile, SOX4 overexpression reversed the effect of up-regulation of miR-212-3p on EC970 function.Conclusions: miR-212-3p mediates the apoptosis and invasion of ESCC cells through inhibiting the Wnt/ β-catenin signal pathway by targeting SOX4.

Correlation of SOX4, SOX17, VE-cadherin and vasculogenic mimicry with prognosis in esophageal squamous cell carcinoma

“…The SOX17 transcription factor has been known to have tumor suppressive function in ESCC [35][36][37]. SOX17 overexpression suppresses colony formation and cell migration/invasion in ESCC cell lines.…”

Identification and Validation of Novel Diagnostic Biomarkers for Keloid Based on GEO Database

“…miR-212-3p regulates cancer tumorigenesis, differentiation, proliferation, and survival by inhibiting major genes, including SGK3, SOX4, SOX11, SOX5. [20][21][22][23][24] There are currently no reports in literature for the function of miR-212-3p on keloid. Unlike miR-212-3p, CCNB1 and CCNB2 alterations may contribute to keloid formation via dysregulation of cell cycle and p53 signaling pathways.…”

Correlation of SOX4, SOX17, VE-cadherin and vasculogenic mimicry with the development and prognosis of esophageal squamous cell carcinoma

“…Based on the ndings of the present study, we rmly believe that VE-cadherin promotes the formation of VM in ESCC. The SOX17 transcription factor has been known to have tumor suppressive function in ESCC [35][36][37]. SOX17 overexpression suppresses colony formation and cell migration/invasion in ESCC cell lines.…”

“…SOX4 has been found to be involved in tumorigenesis and tumor invasion in different types of cancers through the activated Wnt, transforming growth factor (TGF)-β, Hedgehog and Notch pathways or the regulation of microRNA expression [30]. Zilong et al speculated that miR-212-3p targets SOX4 to inhibit the Wnt/β-catenin signaling pathway and promote apoptosis in ESCC [37].…”