Deep sequencing-based microRNA expression signatures in head and neck squamous cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs
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Keiichi Koshizuka1,2, Nijiro Nohata3, Toyoyuki Hanazawa2, Naoko Kikkawa2, Takayuki Arai1, Atsushi Okato1, Ichiro Fukumoto1,2, Koji Katada2, Yoshitaka Okamoto2, Naohiko Seki1
1Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan
2Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
3Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
Naohiko Seki, email: [email protected]
Keywords: microRNA, miR-150, ITGA3, ITGA6, TNC
Received: January 17, 2017 Accepted: March 09, 2017 Published: March 17, 2017
We adopted into RNA-sequencing technologies to construct the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Our signature revealed that a total of 160 miRNAs (44 upregulated and 116 downregulated) were aberrantly expressed in cancer tissues. Expression of miR-150-5p (guide strand miRNA) and miR-150-3p (passenger strand miRNA) were significantly silenced in cancer tissues, suggesting both miRNAs act as antitumor miRNAs in HNSCC cells. Ectopic expression of mature miRNAs, miR-150-5p and miR-150-3p inhibited cancer cell aggressiveness. Low expression of miR-150-5p and miR-150-3p predicted significantly shorter overall survival in patients with HNSCC (P = 0.0091 and P = 0.0386) by Kaplan–Meier survival curves analyses. We identified that integrin α3 (ITGA3), integrin α6 (ITGA6), and tenascin C (TNC) were coordinately regulated by these miRNAs in HNSCC cells. Knockdown assays using siRNAs showed that ITGA3, ITGA6 and TNC acted as cancer promoting genes in HNSCC cells. Moreover, ITGA3, ITGA6, and TNC alterations were associated with significantly poorer overall survival (P = 0.0177, P = 0.0237, and P = 0.026, respectively). Dual strands of pre-150 (miR-150-5p and miR-150-3p) functioned as antitumor miRNAs based on the miRNA expression signature of HNSCC. Identification of antitumor miR-150-mediated RNA networks may provide novel insights into pathogenesis of HNSCC.
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