Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2
Objective: Type 2 diabetes mellitus (T2DM) is thought to be a risk factor for endometrial hyperplasia, but potential links between the two diseases are unknown. This study aims to evaluate the role of T2DM in the progression of endometrial hyperplasia. Methods: Female Sprague-Dawley rats were random...
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2020-11-01
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doaj-cc18342853674f7f8d1d9a15eb1f9b3e2021-05-20T07:44:04ZengElsevierBiomedicine & Pharmacotherapy0753-33222020-11-01131110764Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2Xueyan Zhou0Yinxue Xu1Di Yin2Feng Zhao3Zhixiang Hao4Ya’nan Zhong5Jingbo Zhang6Bei Zhang7Xiaoxing Yin8Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, ChinaDepartment of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, ChinaDepartment of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China; Corresponding author at: Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, 199 South Jiefang Road, Xuzhou 221004, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China; Corresponding author at: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, China.Objective: Type 2 diabetes mellitus (T2DM) is thought to be a risk factor for endometrial hyperplasia, but potential links between the two diseases are unknown. This study aims to evaluate the role of T2DM in the progression of endometrial hyperplasia. Methods: Female Sprague-Dawley rats were randomly divided into normal (N) group, endometrial hyperplasia (NH) group, T2DM (T) group, and endometrial hyperplasia with T2DM (TH) group. Proteomics analysis was performed to determine the protein profile of endometrial tissues. Proliferation, migration, and invasion of cells with/without GLANT2-knockdown were assessed. Immunohistochemical staining and ELISA were used to examine the expression of GALNT2 in endometrial tissues and serum of clinical samples. Results: The highest uterus index and endometrial thickness were observed in TH group, with the expression of proliferation marker PCNA increased significantly, indicating that T2DM facilitates the progress of endometrial hyperplasia. Proteomics analysis showed that there were significant differences in protein profiles among groups and differential proteins were mainly enriched in metabolic pathways. Further verification by molecular biology analysis indicated that GALNT2 is the key target for T2DM facilitating endometrial hyperplasia. The expression of GALNT2 was significantly decreased in high glucose environment. T2DM could synergize the proliferative function of GALNT2 aberration by activating EGFR/AKT/ERK pathway. The decreased expressions of GALNT2 in clinical samples were associated with worse subtypes of endometrial hyperplasia. Conclusion: T2DM promoted the progression of endometrial hyperplasia by regulating the GALNT2-mediated phosphorylation of EGFR and enhancing cell proliferation. GALNT2 has the potential to be a novel biomarker in the treatment of endometrial hyperplasia.http://www.sciencedirect.com/science/article/pii/S0753332220309574Type 2 diabetes mellitusEndometrial hyperplasiaEndometrial cancerN-Acetylgalactosaminyltransferase 2Epidermal growth factor receptorProteomics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xueyan Zhou Yinxue Xu Di Yin Feng Zhao Zhixiang Hao Ya’nan Zhong Jingbo Zhang Bei Zhang Xiaoxing Yin |
spellingShingle |
Xueyan Zhou Yinxue Xu Di Yin Feng Zhao Zhixiang Hao Ya’nan Zhong Jingbo Zhang Bei Zhang Xiaoxing Yin Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2 Biomedicine & Pharmacotherapy Type 2 diabetes mellitus Endometrial hyperplasia Endometrial cancer N-Acetylgalactosaminyltransferase 2 Epidermal growth factor receptor Proteomics |
author_facet |
Xueyan Zhou Yinxue Xu Di Yin Feng Zhao Zhixiang Hao Ya’nan Zhong Jingbo Zhang Bei Zhang Xiaoxing Yin |
author_sort |
Xueyan Zhou |
title |
Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2 |
title_short |
Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2 |
title_full |
Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2 |
title_fullStr |
Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2 |
title_full_unstemmed |
Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2 |
title_sort |
type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin o-glycosylating enzyme galnt2 |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2020-11-01 |
description |
Objective: Type 2 diabetes mellitus (T2DM) is thought to be a risk factor for endometrial hyperplasia, but potential links between the two diseases are unknown. This study aims to evaluate the role of T2DM in the progression of endometrial hyperplasia. Methods: Female Sprague-Dawley rats were randomly divided into normal (N) group, endometrial hyperplasia (NH) group, T2DM (T) group, and endometrial hyperplasia with T2DM (TH) group. Proteomics analysis was performed to determine the protein profile of endometrial tissues. Proliferation, migration, and invasion of cells with/without GLANT2-knockdown were assessed. Immunohistochemical staining and ELISA were used to examine the expression of GALNT2 in endometrial tissues and serum of clinical samples. Results: The highest uterus index and endometrial thickness were observed in TH group, with the expression of proliferation marker PCNA increased significantly, indicating that T2DM facilitates the progress of endometrial hyperplasia. Proteomics analysis showed that there were significant differences in protein profiles among groups and differential proteins were mainly enriched in metabolic pathways. Further verification by molecular biology analysis indicated that GALNT2 is the key target for T2DM facilitating endometrial hyperplasia. The expression of GALNT2 was significantly decreased in high glucose environment. T2DM could synergize the proliferative function of GALNT2 aberration by activating EGFR/AKT/ERK pathway. The decreased expressions of GALNT2 in clinical samples were associated with worse subtypes of endometrial hyperplasia. Conclusion: T2DM promoted the progression of endometrial hyperplasia by regulating the GALNT2-mediated phosphorylation of EGFR and enhancing cell proliferation. GALNT2 has the potential to be a novel biomarker in the treatment of endometrial hyperplasia. |
topic |
Type 2 diabetes mellitus Endometrial hyperplasia Endometrial cancer N-Acetylgalactosaminyltransferase 2 Epidermal growth factor receptor Proteomics |
url |
http://www.sciencedirect.com/science/article/pii/S0753332220309574 |
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