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.

Tian-Yu Liu,Chun-Liang Shang,Jian Chen,Jia-Ming Huang,Man Shu,Zheng Hu,Yun-He Zhao,Wei Wang,Yan-Chun Liang,Shu-Zhong Yao,Duo Liu,Hong-Wei Shen,Lu-Yan Guo

doi:10.1186/s13046-016-0445-5

Abstract

BackgroundTRIM62 (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).MethodsQuantitative 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.ResultsTRIM62 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.ConclusionTRIM62 is a potential prognostic biomarker in CC and suppresses metastasis of CC via inhibiting c-Jun/Slug signaling-mediated EMT.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0445-5) contains supplementary material, which is available to authorized users.

Highlights

Tripartite motif containing 62 (TRIM62) has been found to act as a tumor suppressor of several cancers
To determine whether TRIM62 was lowly expressed in CC tissues, firstly 20 normal cervical tissue (NCT) and 40 earlystage CC tissues were selected for quantitative realtime PCR (qRT-PCR)
The results showed that TRIM62 was less expressed in early-stage CC tissues, compared with NCT, both protein and messenger RNA (mRNA) level. (Fig. 1c and Fig. 1d)

Summary

Introduction

TRIM62 (tripartite motif containing 62) has been found to act as a tumor suppressor of several cancers. Its precise biological role and related mechanism remain unknown in cervical cancer (CC). Cervical cancer (CC) is one of the most common malignant tumors in women. There are still approximately 527,600 new cases and 265,700 deaths worldwide in 2012. In China, there were about 98,900 new cases and 30,500 deaths among 2015 [3]. It has been well known that tumor recurrence and metastasis has become the major obstacle to improve the long-term survival of CC [4, 5]. Persistent infection of highrisk human papillomavirus (HPV) is confirmed to be associated with the development of the majority of CC [9, 10], the molecular mechanism underlying cervical carcinogenesis and tumor progression remain unclear and there has been no accurate biomarker for predicting aggressiveness and prognosis of CC so far.

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