SNHG17, as an EMT‐related lncRNA, promotes the expression of c‐Myc by binding to c‐Jun in esophageal squamous cell carcinoma

• Published in: Cancer science 2022-01, Vol.113 (1), p.319-333
• Main Authors: Shen, Supeng, Liang, Jia, Liang, Xiaoliang, Wang, Gaoyan, Feng, Bo, Guo, Wei, Guo, Yanli, Dong, Zhiming
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Apoptosis; Binding sites; Cancer therapies; Cell activation; Cell cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chromatin; c‐Myc; EMT; Epithelial-Mesenchymal Transition; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; esophageal squamous cell carcinoma; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - pathology; Esophagus; Female; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Growth factors; Humans; Immunoprecipitation; Jun protein; Male; Medical prognosis; Mesenchyme; Metastasis; Mice; Myc protein; Neoplasm Staging; Neoplasm Transplantation; Original; Pathogenesis; Plasmids; Prostate cancer; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-myc - genetics; Reagents; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; SNHG17; Squamous cell carcinoma; Therapeutic targets; Transcription; Tumors; Up-Regulation
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15184

Dysregulation of long noncoding RNA SNHG17 is associated with the occurrence of several tumors; however, its role in esophageal squamous cell carcinoma (ESCC) remains obscure. The present study demonstrated that SNHG17 was upregulated in ESCC tissues and cell lines, induced by TGF‐β1, and associated with poor survival. It is also involved in the epithelial‐to‐mesenchymal transition (EMT) process. The mechanism underlying SNHG17‐regulated c‐Myc was detected by RNA immunoprecipitation, RNA pull‐down, chromatin immunoprecipitation, and luciferase reporter assays. SNHG17 was found to directly regulate c‐Myc transcription by binding to c‐Jun protein and recruiting the complex to specific sequences of the c‐Myc promoter region, thereby increasing its expression. Moreover, SNHG17 hyperactivation induced by TGF‐β1 results in PI3K/AKT pathway activation, promoting cells EMT, forming a positive feedback loop. Furthermore, SNHG17 facilitated ESCC tumor growth in vivo. Overall, this study demonstrated that the SNHG17/c‐Jun/c‐Myc axis aggravates ESCC progression and EMT induction by TGF‐β1 and may serve as a new therapeutic target for ESCC. SNHG17 was upregulated and associated with poor survival in ESCC. TGF‐β1 induced SNHG17 involved in the epithelial‐to‐mesenchymal transition process and activated the PI3K/AKT pathway. Mechanistically, SNHG17 was found to directly regulate c‐Myc transcription by binding to c‐Jun protein and recruiting the complex to specific sequences of the c‐Myc promoter region. SNHG17 aggravated ESCC growth in vivo.