MicroRNA-106b is involved in transforming growth factor β1-induced cell migration by targeting disabled homolog 2 in cervical carcinoma

被引：39

作者：

Cheng, Yuan ^{[1
]}

Guo, Yanli ^{[1
]}

Zhang, Youyi ^{[2
,3
]}

You, Ke ^{[1
]}

Li, Zijian ^{[2
,3
]}

Geng, Li ^{[1
]}

机构：

[1] Peking Univ, Dept Gynecol & Obstet, Hosp 3, Beijing 100191, Peoples R China

[2] Peking Univ, Beijing Key Lab Cardiovasicular Receptors Res, Inst Vasc Med,Hosp 3,Minist Hlth, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing 100191, Peoples R China

[3] Peking Univ, Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China

来源：

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2016年 / 35卷

基金：

中国国家自然科学基金;

关键词：

MicroRNA-106b; Cervical cancer; Transforming growth factor beta 1; Disabled homolog 2; CANCER-ASSOCIATED FIBROBLASTS; TUMOR-SUPPRESSOR GENE; DOWN-REGULATION; MESENCHYMAL TRANSITION; MELANOMA-CELLS; BREAST-CANCER; INVASION; METASTASIS; PTEN; BETA;

D O I：

10.1186/s13046-016-0290-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background: MicroRNA-106b (miR-106b) was recently identified as an oncogene participating in cancer progression. Transforming growth factor beta 1(TGF-beta 1) is an indispensable cytokine regulating the local microenvironment, thereby promoting cervical cancer progression. However, the roles of miR-106b in cervical carcinoma progression and TGF-beta 1-involvement in the tumorigenesis of cervical cancer remain unknown. Methods: The expression of miR-106b in human cervical specimens was detected by real-time PCR analysis and in situ hybridization assay. The effect of miR-106b on cell migration was analyzed by scratch and transwell assays. TGF-beta 1 was used to induce cell migration. The expression of the miR-106b target gene DAB2 in human cervical tissues and cell lines were measured by qRT-PCR, western blot and immunohistochemistry. Dual-luciferase reporter assay was used to identify DAB2 as a miR-106b-directed target gene. Results: miR-106b was frequently up-regulated in human cervical carcinoma specimens and cervical cancer cell lines. Over-expression of miR-106b significantly promoted HeLa and SiHa cells migration. Likewise, inhibition of miR-106b decreased HeLa and SiHa cells migration. The multifunctional cytokine TGF-beta facilitates metastasis in cervical carcinoma. miR-106b inhibitor treatment decreased the TGF-beta 1-stimulated migration of HeLa and SiHa cells. DAB2, a predicted target gene of miR-106b, was inhibited by TGF-beta 1 partly through miR-106b and was involved in TGF-beta 1-induced cervical cancer cell migration. The expression of DAB2 was low in cervical cancer tissues, and negatively correlated with miR-106b expression. Finally, DAB2 was identified as a miR-106b-directed target gene by dual-luciferase reporter assay. Conclusion: Our data suggest that the TGF-beta 1/miR-106b/DAB2 axis may be involved in the pathogenesis of cervical carcinoma.

引用

页数：11

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