Tumour Suppressive MicroRNA-874 Regulates Novel Cancer Networks in Maxillary Sinus Squamous Cell Carcinoma

Overview

Journal Br J Cancer

Specialty Oncology

Date 2011 Aug 18

PMID 21847129

Citations 58

Authors

N Nohata

T Hanazawa

N Kikkawa

D Sakurai

L Fujimura

T Chiyomaru

K Kawakami

H Yoshino

H Enokida

M Nakagawa

A Katayama

Y Harabuchi

Y Okamoto

N Seki

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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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