Tripartite Motif Containing 62 is a Novel Prognostic Marker and Suppresses Tumor Metastasis Via C-Jun/Slug Signaling-mediated Epithelial-mesenchymal Transition in Cervical Cancer

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2016 Oct 30

PMID 27793172

Citations 17

Authors

Tian-Yu Liu

Jian Chen

Chun-Liang Shang

Hong-Wei Shen

Jia-Ming Huang

Yan-Chun Liang

Wei Wang

Yun-He Zhao

Duo Liu

Man Shu

Lu-Yan Guo

Zheng Hu

Shu-Zhong Yao

Affiliations

Soon will be listed here.

Abstract

Background: TRIM62 (tripartite motif containing 62) has been found to act as a tumor suppressor of several cancers. However, its precise biological role and related mechanism remain unknown in cervical cancer (CC).

Methods: Quantitative Real-time PCR and western blot were adopted to detect the mRNA and protein expression level of TRIM62 in both human CC cell lines and tissues. Immunohistochemistry was used to measure the TRIM62 expression in 30 normal cervical and 189 CC tissues. Univariate and multivariate Cox regression analyses and Kaplan-Meier survival analyses performed to investigate the association between TRIM62 expression and CC patients' prognosis. The effect of TRIM62 on CC growth and metastasis was studied in vitro and in vivo. Multi-pathway reporter array were utilized to identify the potential signaling manipulated by TRIM62.

Results: TRIM62 was frequently down-regulated in both human CC cells and tissues. Low expression of TRIM62 in CC tissues was associated with aggressive clinicopathological features of CC patients. In addition, TRIM62 was also an independent poor prognostic factor for overall and disease-free survival of CC patients after surgery. Moreover, enforced expression of TRIM62 in CC cells significantly inhibited their abilities of proliferation, migration and invasion in vitro. Besides, subcutaneous xenograft tumor model and xenograft mouse metastatic model respectively displayed that TRIM62 impeded the growth and metastasis of CC in vivo. Furthermore, mechanism study exhibited that TRIM62 could suppress epithelial-mesenchymal transition (EMT) by inhibiting c-Jun/Slug signaling. The inhibitory role of TRIM62 in tumor proliferation might be through regulating cell cycle related proteins CyclinD1 and P27 by targeting c-Jun.

Conclusion: TRIM62 is a potential prognostic biomarker in CC and suppresses metastasis of CC via inhibiting c-Jun/Slug signaling-mediated EMT.

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