Deep sequencing-based microRNA expression signatures in head and neck squamous cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs

// Keiichi Koshizuka 1, 2 , Nijiro Nohata 3 , Toyoyuki Hanazawa 2 , Naoko Kikkawa 2 , Takayuki Arai 1 , Atsushi Okato 1 , Ichiro Fukumoto 1, 2 , Koji Katada 2 , Yoshitaka Okamoto 2 , Naohiko Seki 1 1 Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan 2 Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan 3 Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA Correspondence to: Naohiko Seki, email: naoseki@faculty.chiba-u.jp Keywords: microRNA, miR-150, ITGA3, ITGA6, TNC Received: January 17, 2017 Accepted: March 09, 2017 Published: March 17, 2017 ABSTRACT 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.