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
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
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DOI：
10.1038/jhg.2015.120
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发表时间：
2016-02-01
影响因子：
3.5
通讯作者：
Seki, Naohiko
中科院分区：
文献类型：
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作者：
Fukumoto, Ichiro;Kikkawa, Naoko;Seki, Naohiko
尽管包括手术、放疗和化疗在内的综合治疗取得了相当大的进展，但头颈部鳞状细胞癌（HNSCC）患者的总体生存率非常低（仅15 - 45%）。利用目前可用的基因组方法了解HNSCC转移途径的分子机制可能会改善该疾病的治疗和预防。我们前期的研究表明，miR-26 a/B、miR-29 a/B/c和miR-218三种肿瘤抑制性microRNAs（microRNAs）能显著抑制癌细胞的迁移和侵袭。因此，我们假设这些miRNA调控的靶基因对癌症转移有很大贡献。这些肿瘤抑制性miRNA通过使用计算机分析和荧光素酶报告基因测定直接调节HNSCC细胞中的LOXL2表达。在HNSCC临床标本中证实了过表达的LOXL2，并且LOXL2的沉默抑制了HNSCC细胞系中的癌细胞迁移和侵袭。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。
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.