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

Ding, Jie; Huang, Shenglin; Wu, Sen; Zhao, Yingjun; Liang, Linhui; Yan, Mingxia; Ge, Chao; Yao, Jian; Chen, Taoyang; Wan, Dafang; Wang, Hongyang; Gu, Jianren; Yao, Ming; Li, Jinjun; Tu, Hong; He, Xianghuo

doi:10.1038/ncb2039

Cited by 278 publications

(249 citation statements)

References 60 publications

Supporting

Mentioning

239

Contrasting

Order By: Relevance

“…Therefore, developing an effective intervention targeting metastatic disease should improve the mortality of cancer patients. Mounting evidence suggests an important role for miRNAs in the regulation of cancer metastasis, including miR-31, 20 miR-151, 26 miR-34a, 27 miR-146a 17 and miR-92a. 28 However, the functional role of miRNAs in GC metastasis is still largely unknown.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

et al. 2011

View full text Add to dashboard Cite

Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour development and progression. However, little is known about the potential role of miRNAs in gastric cancer (GC) metastasis. In this study, miR-409-3p was found to be downregulated frequently in human GCs, and its expression was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Enforced expression of miR-409 in GC cells significantly reduced their migration and invasion in vitro and their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Moreover, we found that miR-409 exerted its function predominantly through the mature miR-409-3p, but not miR-409-5p. Microarray and bioinformatics analysis identified the pro-metastatic gene radixin (RDX) as a potential miR-409-3p target. Further studies confirmed that miR-409-3p suppressed the expression of RDX by directly binding to its 3 0 -untranslated region. Silencing of RDX by small interfering RNAs phenocopied the effects of miR-409 overexpression, whereas restoration of RDX in miR-409-overexpressed GC cells reversed the suppressive effects of miR-409. Taken together, these results demonstrate that miR-409 suppresses GC cell invasion and metastasis by directly targeting RDX and that patients with downregulated miR-409-3p are prone to lymph node metastasis.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Rho GTPases are activated by the exchange of bound GDP for ambient GTP, which is stimulated by guanine nucleotide exchange factors (GEF) and are inactivated by hydrolysis of bound GTP to GDP catalyzed by GTPase-activating proteins (GAP; 36). This activity cycle is regulated by GDIs, which act to sterically shield the Rho GTPases from the action of GEFs and GAPs (37,38). Recent studies indicate that RhoGDI1 functions as a candidate metastasis suppressor, which is frequently downregulated in hepatocellular carcinoma and breast cancer (37,38).…”

Section: Discussionmentioning

confidence: 99%

“…This activity cycle is regulated by GDIs, which act to sterically shield the Rho GTPases from the action of GEFs and GAPs (37,38). Recent studies indicate that RhoGDI1 functions as a candidate metastasis suppressor, which is frequently downregulated in hepatocellular carcinoma and breast cancer (37,38). Our findings showed that RhoGDI1 is a direct and functional target for miR-483-5p, which can directly suppress RhoGDI1 expression and, thus, in turn activate Rac1 and Cdc42.…”

Section: Discussionmentioning

confidence: 99%

miR-483-5p Promotes Invasion and Metastasis of Lung Adenocarcinoma by Targeting RhoGDI1 and ALCAM

et al. 2014

View full text Add to dashboard Cite

The nodal regulatory properties of microRNAs (miRNA) in metastatic cancer may offer new targets for therapeutic control. Here, we report that upregulation of miR-483-5p is correlated with the progression of human lung adenocarcinoma. miR-483-5p promotes the epithelial-mesenchymal transition (EMT) accompanied by invasive and metastatic properties of lung adenocarcinoma. Mechanistically, miR-483-5p is activated by the WNT/b-catenin signaling pathway and exerts its prometastatic function by directly targeting the Rho GDP dissociation inhibitor alpha (RhoGDI1) and activated leukocyte cell adhesion molecule (ALCAM), two putative metastasis suppressors. Furthermore, we found that downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. Importantly, miR-483-5p levels are positively correlated with b-catenin expression, but are negatively correlated with the levels of RhoGDI1 and ALCAM in human lung adenocarcinoma. Our findings reveal that miR-483-5p is a critical b-catenin-activated prometastatic miRNA and a negative regulator of the metastasis suppressors RhoGDI1 and ALCAM. Cancer Res; 74(11); 3031-42. Ó2014 AACR.

show abstract

“…Recently, a number of cancer genes have been reported to be associated with the tumor metastasis in HCC, including CLU, KAI1, ROCK2 and TWIST [1][2][3][4]. Furthermore, we have previously identified several microRNAs that play critical roles in HCC metastasis, such as miR-30D, miR-151 and miR-210 [5][6][7]. Additionally, many signaling pathways have also been implicated in the process of HCC metastasis, including RAF/MEK/ERK pathway, WNT/ β-catenin pathway, insulin-like growth factor pathway, hepatocyte growth factor/c-MET pathway and growth factor-regulated angiogenic signaling [8].…”

Section: Introductionmentioning

confidence: 99%

Amplification of MPZL1/PZR promotes tumor cell migration through Src-mediated phosphorylation of cortactin in hepatocellular carcinoma

et al. 2013

Self Cite

View full text Add to dashboard Cite

We have previously identified 1 241 regions of somatic copy number alterations (CNAs) in hepatocellular carcinoma (HCC). In the present study, we found that a novel recurrent focal amplicon, 1q24.1-24.2, targets the MPZL1 gene in HCC. Notably, there is a positive correlation between the expression levels of MPZL1 and intrahepatic metastasis of the HCC specimens. MPZL1 can significantly enhance the migratory and metastatic potential of the HCC cells. Moreover, we found that one of the mechanisms by which MPZL1 promotes HCC cell migration is by inducing the phosphorylation and activation of the pro-metastatic protein, cortactin. Additionally, we found that Src kinase mediates the phosphorylation and activation of cortactin induced by MPZL1 overexpression. Taken together, these findings suggest that MPZL1 is a novel pro-metastatic gene targeted by a recurrent region of copy number amplification at 1q24.1-24.2 in HCC.

show abstract

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

Cited by 278 publications

References 60 publications

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

miR-483-5p Promotes Invasion and Metastasis of Lung Adenocarcinoma by Targeting RhoGDI1 and ALCAM

Amplification of MPZL1/PZR promotes tumor cell migration through Src-mediated phosphorylation of cortactin in hepatocellular carcinoma

Contact Info

Product

Resources

About