PMID- 31957155
OWN - NLM
STAT- MEDLINE
DCOM- 20200305
LR  - 20211204
IS  - 1365-2184 (Electronic)
IS  - 0960-7722 (Print)
IS  - 0960-7722 (Linking)
VI  - 53
IP  - 2
DP  - 2020 Feb
TI  - SPAG5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via 
      SPAG5/AKT/mTOR pathway.
PG  - e12738
LID - 10.1111/cpr.12738 [doi]
LID - e12738
AB  - OBJECTIVES: Podocyte injury is a prediction marker of diabetic nephropathy (DN), 
      and AKT/mTOR pathway-mediated inhibition of autophagy is widely reported to 
      contribute to podocyte damage. Recent study stated that sperm-associated antigen 
      5 (SPAG5) activated AKT/mTOR signalling in bladder urothelial carcinoma, 
      indicating SPAG5 might regulate autophagy and play a role in podocyte damage. 
      MATERIALS AND METHODS: Apoptosis and autophagy of human podocytes (HPCs) were 
      detected by flow cytometry and immunofluorescence (IF). Gene level was assessed 
      by Western blot and RT-qPCR. Molecular interactions were determined by pulldown, 
      RNA immunoprecipitation (RIP), co-immunoprecipitation (co-IP), chromatin 
      immunoprecipitation (ChIP) and luciferase reporter assays. RESULTS: SPAG5 mRNA 
      and protein levels were upregulated under high glucose treatment in HPCs. 
      Silencing SPAG5 reversed the increase of apoptosis and decrease of autophagy in 
      high glucose-treated HPCs. Later, we found a long non-coding RNA (lncRNA) SPAG5 
      antisense RNA1 (SPAG5-AS1) as a neighbour gene to SPAG5. Mechanistically, YY1 
      transcriptionally upregulated SPAG5-AS1 and SPAG5 in high glucose-treated 
      podocytes. SPAG5-AS1 acted as a competitive endogenous RNA (ceRNA) to regulate 
      miR-769-5p/YY1 axis and induce SPAG5. SPAG5-AS1 interacted with 
      ubiquitin-specific peptidase 14 (USP14) and leads to de-ubiquitination and 
      stabilization of SPAG5 protein. CONCLUSIONS: This study revealed that SPAG5-AS1 
      inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR 
      pathway, indicating SPAG5-AS1/SPAG5 as a potential target for the alleviation of 
      podocyte injury and offering new thoughts for the treatments of DN.
CI  - (c) 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.
FAU - Xu, Jun
AU  - Xu J
AUID- ORCID: 0000-0002-1576-3882
AD  - Department of Geriatrics, Shanghai Jiao Tong University Affiliated Sixth People's 
      Hospital, Shanghai, China.
FAU - Deng, Yujie
AU  - Deng Y
AD  - Department of Endocrinology, The Affiliated Hospital of Qingdao University, 
      Qingdao, China.
FAU - Wang, Yi
AU  - Wang Y
AD  - Department of Nephrology, Yueyang Hospital of Integrated Traditional Chinese and 
      Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 
      China.
FAU - Sun, Xiaofang
AU  - Sun X
AD  - Department of Endocrinology, The Affiliated Hospital of Qingdao University, 
      Qingdao, China.
FAU - Chen, Shuqin
AU  - Chen S
AD  - Department of Endocrinology and Metabolism, Ningbo First Hospital, Ningbo, China.
FAU - Fu, Guoxiang
AU  - Fu G
AD  - Department of Geriatrics, Shanghai Jiao Tong University Affiliated Sixth People's 
      Hospital, Shanghai, China.
LA  - eng
GR  - 81600684/National Natural Fund Youth Project/
GR  - 81603476/National Natural Fund Youth Project/
GR  - ZR2016HQ16/Youth Fund Project of Shandong Natural Science Foundation/
GR  - 81871092/National Nature Foundation Project/
PT  - Journal Article
DEP - 20200119
PL  - England
TA  - Cell Prolif
JT  - Cell proliferation
JID - 9105195
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (SPAG5 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Autophagy/*physiology
MH  - Cell Cycle Proteins/*metabolism
MH  - Cells, Cultured
MH  - Diabetic Nephropathies/metabolism/pathology
MH  - Glucose/metabolism
MH  - Humans
MH  - Podocytes/*metabolism/physiology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RNA, Long Noncoding/metabolism
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transcription, Genetic/physiology
MH  - Ubiquitin Thiolesterase/metabolism
MH  - Ubiquitination/physiology
MH  - Up-Regulation/physiology
PMC - PMC7046304
OTO - NOTNLM
OT  - AKT/mTOR
OT  - SPAG5
OT  - SPAG5-AS1
OT  - autophagy
OT  - diabetic nephropathy
OT  - podocyte injury
COIS- None.
EDAT- 2020/01/21 06:00
MHDA- 2020/03/07 06:00
PMCR- 2020/01/19
CRDT- 2020/01/21 06:00
PHST- 2019/09/12 00:00 [received]
PHST- 2019/10/26 00:00 [revised]
PHST- 2019/11/14 00:00 [accepted]
PHST- 2020/01/21 06:00 [pubmed]
PHST- 2020/03/07 06:00 [medline]
PHST- 2020/01/21 06:00 [entrez]
PHST- 2020/01/19 00:00 [pmc-release]
AID - CPR12738 [pii]
AID - 10.1111/cpr.12738 [doi]
PST - ppublish
SO  - Cell Prolif. 2020 Feb;53(2):e12738. doi: 10.1111/cpr.12738. Epub 2020 Jan 19.