SP1‐mediated upregulation of lncRNA SNHG4 functions as a ceRNA for miR‐377 to facilitate prostate cancer progression through regulation of ZIC5

• Published in: Journal of cellular physiology 2020-04, Vol.235 (4), p.3916-3927
• Main Authors: Wang, Zhi‐Yong, Duan, Yu, Wang, Peng
• Format: Article
• Language: English
• Subjects: Aged; Apoptosis; Apoptosis - genetics; Assaying; Carcinogenesis - genetics; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Chromatin; Disease Progression; DNA-Binding Proteins - genetics; Flow cytometry; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Immunoprecipitation; lncRNA SNHG4; Lymph nodes; Male; Metastases; Metastasis; MicroRNAs - genetics; Middle Aged; miR‐377; Nucleoli; Polymerase chain reaction; prognosis; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; RNA, Long Noncoding - genetics; snoRNA; Sp1 protein; Sp1 Transcription Factor - genetics; Therapeutic applications; Transcription Factors - genetics; Transcriptional Activation - genetics; Tumorigenesis; Tumors; Up-regulation; Wound healing; ZIC5
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29285

Background/Aims Long noncoding RNAs (lncRNAs) have been demonstrated to serve distinct roles in human tumorigenesis. Previous studies have found that lncRNA small nucleolar RNA host gene 4 (SNHG4) was dysregulated in several tumors. However, the expression, clinical significances, and action mechanisms of SNHG4 in prostate cancer (PCa) are still unclear. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was utilized to detect SNHG4 expression in tissue samples and PCa cells. Cell counting kit‐8, 5‐ethynyl‐2′‐deoxyuridine, clonogenic formation, wound‐healing, and transwell invasion assays were, respectively, used to evaluate cell proliferation, colony formation ability, migration, and invasion. Flow cytometric analysis was applied to assess cell apoptosis. Chromatin immunoprecipitation assays were conducted to determine the binding between SP1 and SNHG4 promoter. Luciferase reporter assay, qRT‐PCR, and western blot analysis were carried out to explore and confirm the interaction among SNHG4, miR‐377, and ZIC5. Results SNHG4 was highly expressed in PCa and its upregulation was induced by transcription factor SP1. The high levels of SNHG4 were distinctly associated with tumor stage, lymph node metastasis, and reduced overall survival of patients with PCa. SNHG4 knockdown inhibited the growth, migration, and invasion of PCa cells. In addition, miR‐377 was a target of SNHG4 and ZIC5 was a target gene of miR‐377 in PCa. SNHG4 promoted ZIC5‐mediated growth and metastasis through modulating miR‐377. Conclusion Our findings illuminate how SNHG4 formed a regulatory network to display a tumor‐promotive effect in PCa and revealed that SNHG4 may be a novel therapeutic target and prognostic marker for patients with PCa. Our findings illuminate how SNHG4 formed a regulatory network to display a tumor‐promotive effect in PCa and revealed that SNHG4 may be a novel therapeutic target and prognostic marker for patients with PCa.