The tumor-suppressive microRNA-23b/27b cluster regulates the MET oncogene in oral squamous cell carcinoma

被引：40

作者：

Fukumoto, Ichiro ^{[1
,2
]}

Koshizuka, Keiichi ^{[1
,2
]}

Hanazawa, Toyoyuki ^{[2
]}

Kikkawa, Naoko ^{[2
]}

Matsushita, Ryosuke ^{[3
]}

Kurozumi, Akira ^{[1
]}

Kato, Mayuko ^{[1
]}

Okato, Atsushi ^{[1
]}

Okamoto, Yoshitaka ^{[2
]}

Seki, Naohiko ^{[1
]}

机构：

[1] Chiba Univ, Dept Funct Genom, Grad Sch Med, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan

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

[3] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Urol, Kagoshima, Kagoshima 8908520, Japan

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2016年 / 49卷 / 03期

关键词：

microRNA; miR-23b; miR-27b; oral squamous cell carcinoma; MET; RECEPTOR TYROSINE KINASE; EXPRESSION SIGNATURE; PROGNOSTIC MARKER; PLUS CETUXIMAB; CANCER; HEAD; NECK; PROGRESSION; MICRORNAS; TARGET;

D O I：

10.3892/ijo.2016.3602

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that two clustered miRNAs, microRNA-23b (miR-23b) and microRNA-27b (miR-27b), were significantly reduced in cancer tissues. Few reports have provided functional analyses of these clustered miRNAs in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the functional significance of miR-23b and miR-27b in OSCC and to identify novel miR-23b/27b-mediated cancer pathways and target genes involved in OSCC oncogenesis and metastasis. Expression levels of miR-23b and miR-27b were significantly reduced in OSCC specimens. Restoration of miR-23b or miR-27b in cancer cells revealed that both miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analyses and luciferase reporter assays showed that the receptor tyrosine kinase MET, was directly regulated by these miRNAs. Moreover, downregulating the MET gene by use of siRNA significantly inhibited cell migration and invasion by OSCC cells. The identification of novel molecular pathways regulated by miR-23b and miR-27b may lead to a better understanding of the oncogenesis and metastasis of this disease.

引用

页码：1119 / 1129

页数：11

共 38 条

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