Artigo Acesso aberto Revisado por pares

Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma

2011; Springer Nature; Volume: 105; Issue: 6 Linguagem: Inglês

10.1038/bjc.2011.311

ISSN

1532-1827

Autores

Nijiro Nohata, Toyoyuki Hanazawa, Naoko Kikkawa, Daiju Sakurai, Lisa Fujimura, Takeshi Chiyomaru, Kazumori Kawakami, Hirofumi Yoshino, Hideki Enokida, Masayuki Nakagawa, Akihiro Katayama, Yasuaki Harabuchi, Yoshitaka Okamoto, Naohiko Seki,

Tópico(s)

interferon and immune responses

Resumo

On the basis of the microRNA (miRNA) expression signature of maxillary sinus squamous cell carcinoma (MSSCC), we found that miR-874 was significantly reduced in cancer cells. We focused on the functional significance of miR-874 in cancer cells and identification of miR-874-regulated novel cancer networks in MSSCC.We used PCR-based methods to investigate the downregulated miRNAs in clinical specimens of MSSCC. Our signature analyses identified 23 miRNAs that were significantly reduced in cancer cells, such as miR-874, miR-133a, miR-375, miR-204, and miR-1. We focused on miR-874 as the most downregulated novel miRNA in our analysis.We found potential tumour suppressive functions such as inhibition of cancer cell proliferation and invasion. A molecular target search of miR-874 revealed that PPP1CA was directly regulated by miR-874. Overexpression of PPP1CA was observed in MSSCC clinical specimens. Silencing of the PPP1CA gene significantly inhibited cancer cell proliferation and invasion.The downregulation of miR-874 was a frequent event in MSSCC, which suggests that miR-874 functions as a tumour suppressive miRNA, directly regulating PPP1CA that has a potential role of an oncogene. The identification of novel miR-874-regulated cancer pathways could provide new insights into potential molecular mechanisms of MSSCC oncogenesis.

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