RRC ID 52506
Author Koshizuka K, Hanazawa T, Kikkawa N, Katada K, Okato A, Arai T, Idichi T, Osako Y, Okamoto Y, Seki N.
Title Antitumor miR-150-5p and miR-150-3p inhibit cancer cell aggressiveness by targeting SPOCK1 in head and neck squamous cell carcinoma.
Journal Auris Nasus Larynx
Abstract OBJECTIVE:Our recent studies have revealed that both strands of pre-miRNAs, the guide strand and the passenger strand, are involved in cancer pathogenesis. Analyses of miRNA expression signatures by RNA sequencing in head and neck squamous cell carcinoma (HNSCC) showed that both of the strands of pre-miR-150 (miR-150-5p and miR-150-3p) were significantly downregulated, and that these miRNAs acted as antitumor miRNAs in HNSCC cells. The aim of this study was to identify oncogenic genes in HNSCC cells that were regulated by miR-150-5p and miR-150-3p.
METHODS:Genome-wide gene expression studies, in silico analyses and dual-luciferase reporter assays were carried out to predict miR-150-5p and miR-150-3p regulation in HNSCC cells. Knockdown assay was applied to investigate the functional significance of the target gene. Overall patient survival as a function of target gene expression was estimated by The Cancer Genome Atlas (TCGA) database.
RESULTS:A total of 19 genes were putative targets of both miR-150-5p and miR-150-3p regulation. Among them, SPOCK1 (SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1) was directly regulated by both miRNAs in HNSCC cells. Knockdown studies using si-SPOCK1 showed that expression of SPOCK1 enhanced HNSCC cell aggressiveness. Overexpression of SPOCK1/SPOCK1 was confirmed in HNSCC clinical specimens. Interestingly, analysis of a large number of patients in the TCGA database (n=248) demonstrated that patients with high SPOCK1 expression had significantly shorter survival than did those with low SPOCK1 expression (P=0.0003). Moreover, 15 pathways were identified as SPOCK1-mediated downstream pathways.
CONCLUSION:Downregulation of both strands of pre-miR-150 (miR-150-5p and miR-150-3p) and overexpression of SPOCK1 contribute to the aggressive nature of HNSCC. The involvement of passenger strand miRNA in the regulation of HNSCC pathogenesis is a novel concept in RNA research.
Volume 45(4)
Pages 854-865
Published 2018-8-1
DOI 10.1016/j.anl.2017.11.019
PII S0385-8146(17)30729-0
PMID 29233721
MeSH Aged Aged, 80 and over Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / metabolism Cell Line, Tumor Computer Simulation Down-Regulation Female Gene Expression Profiling Gene Expression Regulation, Neoplastic / genetics* Gene Knockdown Techniques Head and Neck Neoplasms / genetics* Head and Neck Neoplasms / metabolism Humans Male MicroRNAs / genetics* Middle Aged Neoplasm Staging Proteoglycans / genetics* Proteoglycans / metabolism Real-Time Polymerase Chain Reaction Squamous Cell Carcinoma of Head and Neck Survival Rate
IF 1.387
Times Cited 21
Human and Animal Cells SAS(RCB1974) HSC-3(RCB1975)