Tafazzin (TAZ) promotes the tumorigenicity of cervical cancer cells and inhibits apoptosis.

Mei Chen,Peng-Sheng Zheng,Yuan Zhang,Yi-Hsien Hsieh

doi:10.1371/journal.pone.0177171

Mei Chen, Peng-Sheng Zheng + Show 2 more

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https://doi.org/10.1371/journal.pone.0177171

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Abstract

Tafazzin (TAZ) is often aberrantly expressed in some cancers, including rectal cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer cells remains unknown. This study aims to explore the expression and function of TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein in normal cervical tissue (NC, n = 27), high-grade squamous intraepithelial lesions (HSIL, n = 26) and squamous cervical carcinoma (SCC, n = 41) by immunohistochemistry, the expression of TAZ protein gradually increased from NC to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ. In vitro, the cell growth curves and MTT assays showed that TAZ may promote the growth and viability of cervical cancer cells. In vivo, xenografts experiment showed that TAZ may increase tumor-forming ability. The percentage of apoptosis cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken together, this study demonstrated that TAZ is overexpressed in cervical cancer and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis.

Highlights

Cervical cancer is a common cancer that contributes to cancer-related death in females[1]
The expression of TAZ in human normal cervix and various cervical lesions To understand the endogenous TAZ expression in cervical carcinogenesis, we detected the expression of TAZ in 27 normal cervical samples (NC), 26 high-grade squamous intraepithelial lesions (HSIL) and 41 SCC samples by immunohistochemistry
The expression of TAZ protein in 8 fresh NC samples and 8 fresh SCC lesions from patients undergoing surgery was detected by Western blot (Fig 1D), and the level of TAZ expression related to GAPDH was higher in SCC than that in normal cervical tissue (Fig 1E, P

Summary

Introduction

Cervical cancer is a common cancer that contributes to cancer-related death in females[1]. 80% of cervical cancer cases occur in developing countries, where approximately 270,000 women die from cervical cancer annually[2, 3]. Infection with high-risk human papillomaviruses (HPV) is intimately related to the development of cervical cancer, HPV is not sufficient for cervical carcinogenesis and tumor progression[4,5,6]. Researchers have reported that the aggressive and proliferative nature of human cervical cancer is related to various factors that activate oncogenes and inactivate tumor suppressor genes[7,8,9,10,11,12]. The tafazzin (TAZ) gene is located on the distal region of chromosome Xq28 and encodes the tafazzin protein, which has an amino acid sequence homologous to acyltransferases[13]. TAZ is a mitochondrial protein localized in the mitochondrial membrane and plays a critical

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