PMID- 33152927
OWN - NLM
STAT- MEDLINE
DCOM- 20210219
LR  - 20231213
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 131
DP  - 2020 Nov
TI  - Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by 
      activating the proliferative function of mucin O-glycosylating enzyme GALNT2.
PG  - 110764
LID - S0753-3322(20)30957-4 [pii]
LID - 10.1016/j.biopha.2020.110764 [doi]
AB  - 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.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Zhou, Xueyan
AU  - Zhou X
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Xu, Yinxue
AU  - Xu Y
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Yin, Di
AU  - Yin D
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Zhao, Feng
AU  - Zhao F
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Hao, Zhixiang
AU  - Hao Z
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Zhong, Ya'nan
AU  - Zhong Y
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Zhang, Jingbo
AU  - Zhang J
AD  - Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical 
      School of Xuzhou Medical University, Xuzhou, China.
FAU - Zhang, Bei
AU  - Zhang B
AD  - Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical 
      School of Xuzhou Medical University, Xuzhou, China. Electronic address: 
      bettyzhang10@163.com.
FAU - Yin, Xiaoxing
AU  - Yin X
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China. Electronic address: yinxx@xzhmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20201023
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Mucins)
RN  - EC 2.4.1.- (N-Acetylgalactosaminyltransferases)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/physiology
MH  - Diabetes Mellitus, Experimental/*complications/physiopathology
MH  - Diabetes Mellitus, Type 2/*complications/physiopathology
MH  - Disease Progression
MH  - Endometrial Hyperplasia/*etiology/physiopathology
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Glycosylation
MH  - Mucins/*metabolism
MH  - N-Acetylgalactosaminyltransferases/*metabolism
MH  - Phosphorylation/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Polypeptide N-acetylgalactosaminyltransferase
OTO - NOTNLM
OT  - Endometrial cancer
OT  - Endometrial hyperplasia
OT  - Epidermal growth factor receptor
OT  - N-Acetylgalactosaminyltransferase 2
OT  - Proteomics
OT  - Type 2 diabetes mellitus
EDAT- 2020/11/07 06:00
MHDA- 2021/02/20 06:00
CRDT- 2020/11/06 01:01
PHST- 2020/05/09 00:00 [received]
PHST- 2020/09/13 00:00 [revised]
PHST- 2020/09/16 00:00 [accepted]
PHST- 2020/11/06 01:01 [entrez]
PHST- 2020/11/07 06:00 [pubmed]
PHST- 2021/02/20 06:00 [medline]
AID - S0753-3322(20)30957-4 [pii]
AID - 10.1016/j.biopha.2020.110764 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2020 Nov;131:110764. doi: 10.1016/j.biopha.2020.110764. Epub 
      2020 Oct 23.