Fukumoto Ichiro, Kikkawa Naoko, Matsushita Ryosuke, Kato Mayuko, Kurozumi Akira, Nishikawa Rika, Goto Yusuke, Koshizuka Keiichi, Hanazawa Toyoyuki, Enokida Hideki, Nakagawa Masayuki, Okamoto Yoshitaka, Seki Naohiko
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
J Hum Genet. 2016 Feb;61(2):109-18. doi: 10.1038/jhg.2015.120. Epub 2015 Oct 22.
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.
尽管在多模态治疗方面取得了显著进展,包括手术、放疗和化疗,但头颈部鳞状细胞癌(HNSCC)患者的总体生存率仍然很低(仅为15%-45%)。利用现有的基因组学方法了解HNSCC转移途径的分子机制可能会改善该疾病的治疗和预防。我们之前的研究表明,三种肿瘤抑制性微小RNA(miRNA),即miR-26a/b、miR-29a/b/c和miR-218,能显著抑制癌细胞的迁移和侵袭。因此,我们推测这些miRNA调控的靶基因对癌症转移有深远影响。通过计算机分析和荧光素酶报告基因检测,这些肿瘤抑制性miRNA直接调控HNSCC细胞中LOXL2的表达。在HNSCC临床标本中证实了LOXL2的过表达,并且在HNSCC细胞系中沉默LOXL2可抑制癌细胞的迁移和侵袭。我们目前的数据表明,肿瘤抑制性miRNA对LOXL2的调控将为HNSCC转移的新分子机制提供新的见解。