Control of cancer recurrence and metastasis may lead to improvement of HNSCC disease prognosis. Among patients with HNSCC, hypopharyngeal squamous cell carcinoma is one of the most aggressive malignancies and has an extremely low survival rate due to the high rates of locoregional recurrence and distant metastasis.
HNSCC develops in the mucous membranes of the nasopharynx, oral cavity, oropharynx, larynx, and hypopharynx. Identification of antitumor miR-150-mediated RNA networks may provide novel insights into pathogenesis of HNSCC.ĭespite advances in combination therapies involving surgery, radiotherapy, chemotherapy, and currently available molecular-targeted therapy for head and neck squamous cell carcinoma (HNSCC), the survival rate of patients with this disease has not improved. Dual strands of pre-150 ( miR-150-5p and miR-150-3p) functioned as antitumor miRNAs based on the miRNA expression signature of HNSCC.
Moreover, ITGA3, ITGA6, and TNC alterations were associated with significantly poorer overall survival ( P = 0.0177, P = 0.0237, and P = 0.026, respectively). Knockdown assays using siRNAs showed that ITGA3, ITGA6 and TNC acted as cancer promoting genes in HNSCC cells. We identified that integrin α3 ( ITGA3), integrin α6 ( ITGA6), and tenascin C ( TNC) were coordinately regulated by these miRNAs in HNSCC cells. 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.
Ectopic expression of mature miRNAs, miR-150-5p and miR-150-3p inhibited cancer cell aggressiveness. 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. Our signature revealed that a total of 160 miRNAs (44 upregulated and 116 downregulated) were aberrantly expressed in cancer tissues. We adopted into RNA-sequencing technologies to construct the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Received: JanuAccepted: MaPublished: March 17, 2017 Keywords: microRNA, miR-150, ITGA3, ITGA6, TNC 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 1ġDepartment of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, JapanĢDepartment of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, JapanģMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA
0 kommentar(er)
