Abstract
// Pingsheng Cai 2, * , Xuejing Jin 2, 4, * , Hua Zhu 3 , Shupin Zhu 2 , Lijie Wang 2 and Jing Jin 1 1 Institute of Glycobiological Engineering, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Zhejiang, China 2 Department of Obstetrics and Gynecology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang, China 3 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China 4 Present address: Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China * These authors share co-first authorship Correspondence to: Jing Jin, email: jinjing@wmu.edu.cn Keywords: glycine decarboxylase (GLDC); O-GlcNAcylation; OGT; cervical cancer; metastasis Received: November 27, 2017 Accepted: January 03, 2018 Published: January 09, 2018 ABSTRACT Glycine decarboxylase (GLDC) is one of the glycine metabolic enzymes and was reported as a oncogene involved in tumorigenesis of non-small cell lung cancer. However, the function of GLDC in cervical cancer remains unclear. In this study, we determined the increased expression of GLDC in cervical cancer tissues and cell lines. The clinical pathological characters of GLDC revealed that increased GLDC expression was involved in cervical cancer metastasis. Further in vitro experiments confirmed the promotion of GLDC on cervical cancer metastasis. Furthermore, we found that OGT interacted with GLDC and modified GLDC with O-GlcNAcylation in cervical cancer cell lines. In addition, the O-GlcNAcylation of GLDC greatly enhanced its promotion on migration and invasion in vitro and in vivo . The clinical data further demonstrated the promotion of GLDC and OGT on cervical cancer metastasis, and showed that OGT worsened the prognosis of GLDC High patients. Collectively, this study identified OGT-mediated O-GlcNAcylation on GLDC as an essential regulatory mechanism for promoting cervical cancer metastasis, and provided a therapeutic target for metastatic cervical cancer.
Highlights
Cervical cancer is the fourth most prevalent type of cancer among women worldwide, which accounts for 9% (n = 527,600) of incident cases of cancer and 8% (n = 265,700) of total cancer mortality in 2012 [1]
In order to demonstrate the promoting roles of the O-GlcNAcylation on Glycine decarboxylase (GLDC) in cervical cancer metastasis, Figure 1: GLDC expression is increased in cervical cancer. (A) Relative mRNA levels of GLDC in 146 paired cervical cancer tumor and non-tumor samples were determined by Quantitative real-time PCR (qRT-PCR) assays. (B–C) Protein levels of these tissues samples were determined by western blot (WB) and IHC analysis. (D) Relative protein levels of GLDC were determined by qRT-PCR in a normal cervix cell line (End1) and in four cervical cancer cell lines (HT-3, C33A, Caski and HeLa). (E) mRNA levels of GLDC in End1, HT-3, C33A, Caski and HeLa cell lines were determined by qPCR. (F) The relative mRNA levels of GLDC were analyzed in public cervical cancer databases GSE27678 and GSE52903
GLDC is one of the glycine metabolic enzymes and was reported as a oncogene involved in tumorigenesis of nonsmall cell lung cancer (NSCLC) [9, 30]
Summary
The development of early screening and HPV vaccination reduces the mortality rates in recent years [2, 3], the prognosis of patients is still dismal, mainly due to the high incidence of invasiveness and metastasis of cervical cancer [4]. Besides of NSCLC, the increased expression of GLDC was observed in some other cancers www.impactjournals.com/oncotarget including ovarian cancer, seminoma, invasive lobular carcinoma, and breast cancer [9,10,11]. The increased expression of GLDC was reported to be associated with the poor prognosis of phyllodes tumor, thyroid cancer, invasive lobular carcinoma, and metastatic breast cancer [11,12,13,14]. The roles of GLDC in cervical cancer have never been determined
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