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

被引：109

作者：

Nohata, Nijiro ^{[2
]}

Hanazawa, Toyoyuki ^{[2
]}

Kikkawa, Naoko ^{[2
]}

Mutallip, Muradil ^{[2
]}

Sakurai, Daiju ^{[2
]}

Fujimura, Lisa ^{[3
]}

Kawakami, Kazumori ^{[4
]}

Chiyomaru, Takeshi ^{[4
]}

Yoshino, Hirofumi ^{[4
]}

Enokida, Hideki ^{[4
]}

Nakagawa, Masayuki ^{[4
]}

Okamoto, Yoshitaka ^{[2
]}

Seki, Naohiko ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Funct Genom, Chuo Ku, Chiba 2608670, Japan

[2] Chiba Univ, Grad Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Chiba 2608670, Japan

[3] Chiba Univ, Biomed Res Ctr, Chiba 2608670, Japan

[4] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Urol, Kagoshima 890, Japan

来源：

JOURNAL OF HUMAN GENETICS | 2011年 / 56卷 / 08期

关键词：

AEG-1/MTDH; HNSCC; microRNA; miR-375; tumor suppressor; MOLECULAR-BIOLOGY; TARGETING TAGLN2; PROSTATE-CANCER; MIR-133A; EXPRESSION; IDENTIFICATION; PROLIFERATION; HYBRIDIZATION; PATHOGENESIS; PROGRESSION;

D O I：

10.1038/jhg.2011.66

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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. Journal of Human Genetics (2011) 56, 595-601; doi:10.1038/jhg.2011.66; published online 14 July 2011

引用

页码：595 / 601

页数：7

共 40 条

[1]

[Anonymous], UROL ONCOL

[2]

[Anonymous], PROSTATE

[3]

[Anonymous], DIG DIS SCI

[4]

[Anonymous], Mutat Res