Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA

被引：312

作者：

Ding, Jie ^{[1
]}

Huang, Shenglin ^{[1
]}

Wu, Shunquan ^{[1
]}

Zhao, Yingjun ^{[1
,2
]}

Liang, Linhui ^{[1
]}

Yan, Mingxia ^{[3
]}

Ge, Chao ^{[1
]}

Yao, Jian ^{[1
,2
]}

Chen, Taoyang ^{[4
]}

Wan, Dafang ^{[1
]}

Wang, Hongyang ^{[1
]}

Gu, Jianren ^{[1
]}

Yao, Ming ^{[3
]}

Li, Jinjun ^{[1
]}

Tu, Hong ^{[1
]}

He, Xianghuo ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes, Shanghai 200032, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Shanghai 200032, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst, Dept Expt Pathol, Shanghai 200032, Peoples R China

[4] Qi Dong Liver Canc Inst, Qi Dong 226200, Jiangsu, Peoples R China

来源：

NATURE CELL BIOLOGY | 2010年 / 12卷 / 04期

关键词：

FOCAL-ADHESION KINASE; COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN HEPATOCELLULAR-CARCINOMA; ALLELIC IMBALANCE; CLINICOPATHOLOGICAL SIGNIFICANCE; GENETIC ALTERATIONS; PROGNOSTIC VALUE; HETEROZYGOSITY; CANCER; IDENTIFICATION;

D O I：

10.1038/ncb2039

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Recurrent chromosomal aberrations are often observed in hepatocellular carcinoma (HCC), but little is known about the functional non-coding sequences, particularly microRNAs (miRNAs), at the chromosomal breakpoints in HCC. Here we show that 22 miRNAs are often amplified or deleted in HCC. MicroRNA-151 (miR-151), a frequently amplified miRNA on 8q24.3, is correlated with intrahepatic metastasis of HCC. We further show that miR-151, which is often expressed together with its host gene FAK, encoding focal adhesion kinase, significantly increases HCC cell migration and invasion in vitro and in vivo, mainly through miR-151-5p, but not through miR-151-3p. Moreover, miR-151 exerts this function by directly targeting RhoGDIA, a putative metastasis suppressor in HCC, thus leading to the activation of Rac1, Cdc42 and Rho GTPases. In addition, miR-151 can function synergistically with FAK to enhance HCC cell motility and spreading. Thus, our findings indicate that chromosome gain of miR-151 is a crucial stimulus for tumour invasion and metastasis of HCC.

引用

页码：390 / U208

页数：19

共 67 条

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