Dataset Information

TBLR1 is a novel prognostic marker and promotes epithelial-mesenchymal transition in cervical cancer.

ABSTRACT:

Background

Invasion and metastasis remain a critical issue in cervical cancer. However, the underlying mechanism of it in cervical cancer remains unclear. The newly discovered protein, TBLR1, plays a crucial role in regulating various key cellular functions.

Methods

In this study, western blot, real-time RT-PCR, immunohistochemical staining, 3D morphogenesis Matrigel culture, wound healing and Boyden chamber invasion assays, xenografted tumour model, luciferase assays, and chromatin immunoprecipitation assays were used.

Results

The expression of TBLR1 in cervical cancer cell lines and tissues was significantly upregulated at both the RNA and protein levels compared with that in normal cervical cells. Statistical analysis suggested that TBLR1 as an independent prognostic factor was significantly correlated with the clinical stage, survival time and recurrence. Moreover, overexpression of TBLR1 in Hela and Siha cell lines promoted invasion in vitro and in vivo with the increases of the mesenchymal factors vimentin and fibronectin and decreases of the epithelial marker ?-catenin. In contrast, RNAi-mediated knockdown of TBLR1 inhibited epithelial-mesenchymal transition in vitro and in vivo. Further study indicated that this might be mediated via the NF-?B and Wnt/?-Catenin signalling pathway, and involve regulation of Snail and Twist.

Conclusions

The TBLR1 protein may be a prognostic marker in cervical cancer and play an important role in the invasion and metastasis of human cervical cancer.

SUBMITTER: Wang J

PROVIDER: S-EPMC4090741 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

TBLR1 is a novel prognostic marker and promotes epithelial-mesenchymal transition in cervical cancer.

Wang J J Ou J J Guo Y Y Dai T T Li X X Liu J J Xia M M Liu L L He M M

British journal of cancer 20140529 1

<h4>Background</h4>Invasion and metastasis remain a critical issue in cervical cancer. However, the underlying mechanism of it in cervical cancer remains unclear. The newly discovered protein, TBLR1, plays a crucial role in regulating various key cellular functions.<h4>Methods</h4>In this study, western blot, real-time RT-PCR, immunohistochemical staining, 3D morphogenesis Matrigel culture, wound healing and Boyden chamber invasion assays, xenografted tumour model, luciferase assays, and chromat ...[more]

PMID: 24874481

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Project description:ObjectiveTo explore the role of vasohibin-2 (VASH2) in regulation of proliferation and metastasis of cervical cancer cells.MethodsWe analyzed the differentially expressed genes between cervical cancer cells with flotillin-1 overexpression and knockdown by RNA-seq combined with analysis of public databases. The expression levels of VASH2 were examined in normal cervical epithelial cells (HcerEpic), cervical cancer cell lines (HeLa, C-33A, Ca ski, SiHa and MS751) and fresh cervical cancer tissues with different lymph node metastasis status. We further tested the effects of lentivirus-mediated overexpression and interference of VASH2 on proliferation, migration, invasion and lymphatic vessel formation of the cervical cancer cells and detected the expression levels of key epithelial-mesenchymal transition (EMT) markers and TGF-β mRNA.ResultsRNA-seq and analysis of public databases showed that VASH2 expression was significantly upregulated in cervical cancer cells exogenously overexpressing flotillin-1 (P < 0.05) and downregulated in cells with flotillin-1 knockdown (P < 0.05), and was significantly higher in cervical cancer tissues with lymph node metastasis than in those without lymph node metastasis (P < 0.01). In cervical cancer cell lines Ca Ski, SiHa, and MS751 and cervical cancer tissue specimens with lymph node metastasis, VASH2 expression was also significantly upregulated as compared with HcerEpic cells and cervical cancer tissues without lymph node metastasis (P < 0.05). Exogenous overexpression of VASH2 significantly promoted proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells, whereas these abilities were significantly inhibited in cells with VASH2 knockdown (P < 0.05). The cervical cancer cells overexpressing VASH2 showed significant down- regulation of e-cadherin and up- regulation of N-cadherin, Vimentin and VEGF-C, while the reverse changes were detected in cells with VASH2 knockdown (P < 0.05). TGF-β mRNA expression was significantly up-regulated in cervical cancer cells overexpressing VASH2 and down-regulated in cells with VASH2 knockdown (P < 0.001).ConclusionFlotillin-1 may participate in TGF-β signaling pathway-mediated EMT through its down-stream target gene VASH2 to promote the proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells in vitro.

Dataset Information

TBLR1 is a novel prognostic marker and promotes epithelial-mesenchymal transition in cervical cancer.

Background

Methods

Results

Conclusions

Publications

TBLR1 is a novel prognostic marker and promotes epithelial-mesenchymal transition in cervical cancer.

Similar Datasets

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