Identification of novel molecular targets regulated by tumor suppressive miR-1/miR-133a in maxillary sinus squamous cell carcinoma

被引：89

作者：

Nohata, Nijiro ^{[2
]}

Hanazawa, Toyoyuki ^{[2
]}

Kikkawa, Naoko ^{[2
]}

Sakurai, Daiju ^{[2
]}

Sasaki, Keita ^{[3
]}

Chiyomaru, Takeshi ^{[4
]}

Kawakami, Kazumori ^{[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 Canc Ctr, Dept Head & Neck Surg, Chiba 2608717, Japan

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

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2011年 / 39卷 / 05期

关键词：

microRNA; miR-1; miR-133a; tumor suppressor; transgelin; 2; purine nucleoside phosphorylase; maxillary sinus squamous cell carcinoma; CHRONIC LYMPHOCYTIC-LEUKEMIA; BLADDER-CANCER; HEPATOCELLULAR-CARCINOMA; MICRORNA SIGNATURES; EXPRESSION; MIR-133A; PROTEIN; FORODESINE; TRANSGELIN; APOPTOSIS;

D O I：

10.3892/ijo.2011.1096

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Based on our microRNA (miRNA) expression signature analysis of maxillary sinus squamous cell carcinoma (MSSCC), we found that miR-1 and miR-133a were significantly reduced in tumor tissues. Quantitative real-time RT-PCR revealed that the expression levels of miR-1 and miR-133a were significantly downregulated in clinical MSSCC tumor tissues compared with normal tissues. We focused on the functional significance of miR-1 and miR-133a in cancer cells and identification of the novel cancer networks regulated by these miRNAs in MSSCC. Restoration of downregulated miRNAs (miR-1 or miR-133a) in cancer cells revealed that both miRNAs significantly inhibited cancer cell proliferation and induced cell apoptosis. Molecular target identification of these miRNAs showed that transgelin 2 (TAGLN2) and purine nucleoside phosphorylase (PNP) were regulated by miR-1 and miR-133a. Both TAGLN2 and PNP mRNA expression levels were significantly upregulated in clinical MSSCC tumor tissues. Silencing studies of target genes demonstrated that both genes inhibited cancer cell proliferation. The identification of novel miR-1/miR-133a-regulated cancer pathways could provide new insights into potential molecular mechanisms of MSSCC oncogenesis.

引用

页码：1099 / 1107

页数：9

共 42 条

[1] Forodesine has high antitumor activity in chronic lymphocytic leukemia and activates p53-independent mitochondrial apoptosis by induction of p73 and BIM [J].