PMID- 38353742
OWN - NLM
STAT- MEDLINE
DCOM- 20240301
LR  - 20240301
IS  - 1432-0878 (Electronic)
IS  - 0302-766X (Linking)
VI  - 395
IP  - 3
DP  - 2024 Mar
TI  - Long noncoding RNA XIST inhibition promotes Leydig cell apoptosis by acting as a 
      competing endogenous RNA for microRNA-145a-5p that targets SIRT1 in late-onset 
      hypogonadism.
PG  - 285-297
LID - 10.1007/s00441-024-03860-3 [doi]
AB  - Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone 
      levels during late-onset hypogonadism (LOH). Our study was designed to illustrate 
      the regulatory effect of lncRNA XIST on LCs and to clarify its molecular 
      mechanism of action in LOH. The Leydig cells (TM3) was treated by 300 muM H(2)O(2) 
      for 8 h to establish Leydig cell oxidative stress model in vitro. The expression 
      levels of lncRNA XIST in the testicular tissues of patients with LOH were 
      measured using fluorescence in situ hybridization (FISH). The interaction between 
      lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase 
      reporter gene assays. Apoptotic cells and Caspase3 activity were determined by 
      flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. 
      Moreover, histological assessment of testicles in mice was performed by using HE 
      staining and the TUNEL assay was used to determine apoptosis. We found that the 
      lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice 
      and in H(2)O(2)-induced TM3 cells. XIST siRNA significantly promoted apoptosis, 
      enhanced Caspase3 activity and reduced testosterone levels in H(2)O(2)-stimulated 
      TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the 
      effect of XIST-siRNA on H(2)O(2)-induced Leydig cell apoptosis. MiR-145a-5p 
      negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of 
      the miR-145a-5p inhibitor on H(2)O(2) stimulated TM3 cells. The in vivo 
      experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms 
      in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the 
      miR-145a-5p/SIRT1 axis in the progression of LOH.
CI  - (c) 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Urology, Nanjing First Hospital, Nanjing Medical University, No. 68 
      Changle Road, Qinhuai District, Nanjing, 210006, China.
AD  - Department of Andrology, Nanjing Drum Tower Hospital, Affiliated Hospital of 
      Medical School, Nanjing University, No. 321 Zhongshan Road, Gulou District, 
      Nanjing, 210008, China.
FAU - Yang, Yiqiong
AU  - Yang Y
AD  - Department of Emergency, Nanjing Drum Tower Hospital, Affiliated Hospital of 
      Medical School, Nanjing University, Nanjing, 210008, China.
FAU - Xu, Yang
AU  - Xu Y
AD  - Department of Andrology, Nanjing Drum Tower Hospital, Affiliated Hospital of 
      Medical School, Nanjing University, No. 321 Zhongshan Road, Gulou District, 
      Nanjing, 210008, China.
FAU - Xu, Zhipeng
AU  - Xu Z
AD  - Department of Andrology, Nanjing Drum Tower Hospital, Affiliated Hospital of 
      Medical School, Nanjing University, No. 321 Zhongshan Road, Gulou District, 
      Nanjing, 210008, China.
FAU - Zhao, Xiaozhi
AU  - Zhao X
AD  - Department of Andrology, Nanjing Drum Tower Hospital, Affiliated Hospital of 
      Medical School, Nanjing University, No. 321 Zhongshan Road, Gulou District, 
      Nanjing, 210008, China.
FAU - Jia, Ruipeng
AU  - Jia R
AUID- ORCID: 0009-0002-4265-9797
AD  - Department of Urology, Nanjing First Hospital, Nanjing Medical University, No. 68 
      Changle Road, Qinhuai District, Nanjing, 210006, China. m15951950969@163.com.
FAU - Dai, Yutian
AU  - Dai Y
AD  - Department of Andrology, Nanjing Drum Tower Hospital, Affiliated Hospital of 
      Medical School, Nanjing University, No. 321 Zhongshan Road, Gulou District, 
      Nanjing, 210008, China. johnwang0212@sina.com.
LA  - eng
GR  - BE2019606/The Application Value of Penile Neuroelectrophysiological Techniques in 
      the Diagnosis and Treatment of Premature Ejaculation/
PT  - Journal Article
DEP - 20240214
PL  - Germany
TA  - Cell Tissue Res
JT  - Cell and tissue research
JID - 0417625
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Competitive Endogenous)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Small Interfering)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - 3XMK78S47O (Testosterone)
RN  - 0 (XIST non-coding RNA)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - 0 (MIRN145a microRNA, mouse)
RN  - 0 (MIRN145 microRNA, human)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Male
MH  - Mice
MH  - Apoptosis
MH  - Cell Proliferation/genetics
MH  - Hydrogen Peroxide
MH  - *Hypogonadism/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Leydig Cells/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - RNA, Competitive Endogenous
MH  - *RNA, Long Noncoding/genetics/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Sirtuin 1/genetics
MH  - Testosterone/pharmacology
OTO - NOTNLM
OT  - Late-onset hypogonadism
OT  - Leydig cell apoptosis
OT  - lncRNA XIST
OT  - microRNA-145a-5p/SIRT1
EDAT- 2024/02/14 12:43
MHDA- 2024/03/01 06:44
CRDT- 2024/02/14 11:06
PHST- 2023/05/25 00:00 [received]
PHST- 2024/01/04 00:00 [accepted]
PHST- 2024/03/01 06:44 [medline]
PHST- 2024/02/14 12:43 [pubmed]
PHST- 2024/02/14 11:06 [entrez]
AID - 10.1007/s00441-024-03860-3 [pii]
AID - 10.1007/s00441-024-03860-3 [doi]
PST - ppublish
SO  - Cell Tissue Res. 2024 Mar;395(3):285-297. doi: 10.1007/s00441-024-03860-3. Epub 
      2024 Feb 14.