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MLL1 promotes cervical carcinoma cell tumorigenesis and metastasis through interaction with β-catenin

Authors Qiang R, Cai N, Wang X, Wang L, Cui K, Wang X, Li X

Received 5 June 2016

Accepted for publication 15 August 2016

Published 28 October 2016 Volume 2016:9 Pages 6631—6640

DOI https://doi.org/10.2147/OTT.S114370

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Professor Jianmin Xu


Rong Qiang,1,2 Na Cai,2 Xiaobin Wang,2 Lin Wang,2 Ke Cui,2 Xiang Wang,1 Xu Li1

1Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, 2Medical Heredity Research Center, Northwest Women’s and Children’s Hospital, Shaanxi, People’s Republic of China

Abstract: MLL protein genes encode a family of crucial transcription factors that play a key role in multiple cancer development. The functions of different MLL proteins have not been definitively studied. MLL1 is a histone methyltransferase that mediates histone H3 lysine 4, and it has been found to have aberrant expression in several tumors. However, the function of MLL1 in cervical carcinoma is little known. We used tissue analysis, cell culture experiments, and molecular profiling to investigate the mechanism of MLL1 in cervical carcinoma development. We report here that MLL1 is overexpressed in cervical carcinoma tissues and cell lines, and its overexpression is correlated with the tumor grade. Through FACScan flow cytometry assay, we found that MLL1 promotes cell proliferation by promoting the G1/S transition through transcriptional activation of CCND1 in cervical carcinoma cells. Furthermore, we utilized co-immunoprecipitation and glutathione S-transferase pull-down assays to identify β-catenin as the transcription partner for MLL1 and demonstrated that MLL1 and β-catenin act in synergy in the transcriptional activation of CCND1 in cervical carcinoma cells. In addition, transwell assay and anchorage-independent cell growth assay also revealed that MLL1 promotes metastasis of cervical carcinoma cells through interaction with β-catenin. Our study not only demonstrated a role for MLL1 in the proliferation and metastasis of cervical carcinoma cells but also revealed the interaction of MLL1 with β-catenin to play a different role.

Keywords: MLL1, cell cycle, β-catenin, metastasis

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