Open AccessLong noncoding RNA SNHG12 induces proliferation, migration, epithelial–mesenchymal transition, and stemness of esophageal squamous cell carcinoma cells via post‐transcriptional regulation of BMI1 and CTNNB1
Author(s) -
Wu Duoguang,
He Xiaotian,
Wang Wenjian,
Hu Xueting,
Wang Kefeng,
Wang Minghui
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12683
Subject(s) - epithelial–mesenchymal transition , cancer research , long non coding rna , biology , gene silencing , gene knockdown , bmi1 , cell growth , stem cell , oncogene , carcinogenesis , cell migration , cell , metastasis , microbiology and biotechnology , cell culture , cell cycle , downregulation and upregulation , cancer , genetics , gene
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors around the world. Numerous studies have revealed the function of long noncoding RNAs (lncRNAs) in cancers, including ESCC. In this study, lncRNA small nucleolar RNA host gene 12 (SNHG12), mainly distributed in ESCC cell cytoplasm, was overexpressed in ESCC specimens and CD133 + cells. In CD133 ‐ ESCC cells, SNHG12 overexpression promoted cell proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness and SNHG12 silencing led to opposite results. Furthermore, SNHG12 sequestered miR‐6835‐3p and induced the proto‐oncogene, polycomb ring finger (BMI1). SNHG12 also enhanced the stability of CTNNB1, the mRNA encoding β‐catenin, via recruiting insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) in ESCC. Rescue assays indicated that CTNNB1 and BMI1 were targets for SNHG12 to regulate ESCC cell proliferation, migration, EMT, and stemness. Furthermore, SOX4 (sex‐determining region Y‐box 4) bound with the SNHG12 promoter to transcriptionally activate SNHG12 in ESCC. Finally, in vivo data showed SNHG12 knockdown retarded tumorigenesis and metastasis in ESCC. In summary, SNHG12 induces proliferation, migration, EMT, and stemness of ESCC cells via post‐transcriptional regulation of BMI1 and CTNNB1, indicating that targeting SNHG12 might be a novel target for ESCC treatment.