Tumor suppressive microRNA-375 regulates oncogene AEG-1/MTDH in head and neck squamous cell carcinoma (HNSCC).

Abstract

Our microRNA (miRNA) expression signatures of hypopharyngeal squamous cell carcinoma, maxillary sinus squamous cell carcinoma and esophageal squamous cell carcinoma revealed that miR-375 was significantly reduced in cancer tissues compared with normal epithelium. In this study, we focused on the functional significance of miR-375 in cancer cells and identification of miR-375-regulated novel cancer networks in head and neck squamous cell carcinoma (HNSCC). Restoration of miR-375 showed significant inhibition of cell proliferation and induction of cell apoptosis in SAS and FaDu cell lines, suggesting that miR-375 functions as a tumor suppressor. We adopted genome-wide gene expression analysis to search for miR-375-regulated molecular targets. Gene expression data and luciferase reporter assays revealed that AEG-1/MTDH was directly regulated by miR-375. Cancer cell proliferation was significantly inhibited in HNSCC cells transfected with si-AEG-1/MTDH. In addition, expression levels of AEG-1/MTDH were significantly upregulated in cancer tissues. Therefore, AEG-1/MTDH may function as an oncogene in HNSCC. The identification of novel tumor suppressive miRNA and its regulated cancer pathways could provide new insights into potential molecular mechanisms of HNSCC oncogenesis.

• Authors: Nijiro Nohata, Toyoyuki Hanazawa, Naoko Kikkawa, Muradil Mutallip, Daiju Sakurai, Lisa Fujimura, Kazumori Kawakami, Takeshi Chiyomaru, Hirofumi Yoshino, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
• Journal: Journal of human genetics (J Hum Genet) Vol. 56 Issue 8 Pg. 595-601 (Aug 2011) ISSN: 1435-232X [Electronic] England
• PMID: 21753766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• MIRN375 microRNA, human
• MTDH protein, human
• Membrane Proteins
• MicroRNAs
• RNA-Binding Proteins

Topics

• Aged
• Aged, 80 and over
• Base Sequence
• Blotting, Western
• Carcinoma, Squamous Cell (genetics)
• Cell Adhesion Molecules (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genes, Tumor Suppressor
• Head and Neck Neoplasms (genetics)
• Humans
• Male
• Membrane Proteins
• MicroRNAs (genetics)
• Middle Aged
• Molecular Sequence Data
• Oligonucleotide Array Sequence Analysis
• Proto-Oncogenes (genetics)
• RNA Interference
• RNA-Binding Proteins
• Reverse Transcriptase Polymerase Chain Reaction
• Squamous Cell Carcinoma of Head and Neck
• Transfection