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Tumor-suppressive microRNAs (miR-26a/b, miR-29a/b/c and miR-218) concertedly suppressed metastasis-promoting LOXL2 in head and neck squamous cell carcinoma.

Abstract
In spite of considerable advances in multimodality therapy, including surgery, radiotherapy and chemotherapy, the overall survival rate for patients with head and neck squamous cell carcinoma (HNSCC) is very poor (only 15-45%). Understanding the molecular mechanisms of metastatic pathways underlying HNSCC using currently available genomic approaches might improve therapies for and prevention of the disease. Our previous studies showed that three tumor-suppressive microRNAs (miRNAs), miR-26a/b, miR-29a/b/c and miR-218, significantly inhibited cancer cell migration and invasion. Therefore, we hypothesized that these miRNAs-regulated target genes deeply contributed to cancer metastasis. These tumor-suppressive miRNAs directly regulate LOXL2 expression in HNSCC cells by using in silico analysis and luciferase reporter assays. Overexpressed LOXL2 was confirmed in HNSCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in HNSCC cell lines. Our present data showed that tumor-suppressive miRNAs regulation of LOXL2 will provide new insights into the novel molecular mechanisms of HNSCC metastasis.
AuthorsIchiro Fukumoto, Naoko Kikkawa, Ryosuke Matsushita, Mayuko Kato, Akira Kurozumi, Rika Nishikawa, Yusuke Goto, Keiichi Koshizuka, Toyoyuki Hanazawa, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
JournalJournal of human genetics (J Hum Genet) Vol. 61 Issue 2 Pg. 109-18 (Feb 2016) ISSN: 1435-232X [Electronic] England
PMID26490187 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • MIRN218 microRNA, human
  • MIRN26A microRNA, human
  • MIRN29a microRNA, human
  • MicroRNAs
  • Amino Acid Oxidoreductases
  • LOXL2 protein, human
Topics
  • Amino Acid Oxidoreductases (genetics, metabolism)
  • Carcinoma, Squamous Cell (genetics, metabolism, pathology)
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms (genetics, metabolism, pathology)
  • Humans
  • MicroRNAs (metabolism)
  • Squamous Cell Carcinoma of Head and Neck

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