PMID- 36987665
OWN - NLM
STAT- MEDLINE
DCOM- 20230719
LR  - 20230911
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 29
IP  - 8
DP  - 2023 Aug
TI  - Temozolomide protects against the progression of glioblastoma via SOX4 
      downregulation by inhibiting the LINC00470-mediated transcription factor EGR2.
PG  - 2292-2307
LID - 10.1111/cns.14181 [doi]
AB  - OBJECTIVE: Temozolomide is extensively applied in chemotherapy for glioblastoma 
      with unclear exact action mechanisms. This article seeks to address the potential 
      molecular mechanisms in temozolomide therapy for glioblastoma involving 
      LINC00470. METHODS: Bioinformatics analysis was conducted to predict the 
      potential mechanism of LINC00470 in glioblastoma, which was validated by 
      dual-luciferase reporter, RIP, ChIP, and RNA pull-down assays. LINC00470 
      expression and the predicted downstream transcription factor early growth 
      response 2 (EGR2) were detected in the collected brain tissues from glioblastoma 
      patients. Following temozolomide treatment and/or gain- and loss-of-function 
      approaches in glioblastoma cells, cell viability, invasion, migration, cycle 
      distribution, angiogenesis, autophagy, and apoptosis were measured. In addition, 
      the expression of mesenchymal surface marker proteins was assessed by western 
      blot. Tumor xenograft in nude mice was conducted for in vivo validation. RESULTS: 
      Mechanistic analysis and bioinformatics analysis revealed that LINC00470 
      transcriptionally activated SRY-related high-mobility-group box 4 (SOX4) through 
      the transcription factor EGR2. LINC00470 and EGR2 were highly expressed in brain 
      tissues of glioblastoma patients. LINC00470 and EGR2 mRNA expression gradually 
      decreased with increasing concentrations of temozolomide in glioblastoma cells, 
      and SOX4 expression was reduced in cells by temozolomide and LINC00470 knockdown. 
      Temozolomide treatment induced cell cycle arrest, diminished cell viability, 
      migration, invasion, and angiogenesis, and increased apoptosis and autophagy in 
      glioblastoma, which was counteracted by overexpressing LINC00470 or SOX4 but was 
      further promoted by LINC00470 knockdown. Temozolomide restrained glioblastoma 
      growth and angiogenesis in vivo, while LINC00470 or SOX4 overexpression nullified 
      but LINC00470 knockdown further facilitated these trends. CONCLUSION: 
      Conclusively, temozolomide repressed glioblastoma progression by repressing the 
      LINC00470/EGR2/SOX4 axis.
CI  - (c) 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & 
      Sons Ltd.
FAU - Li, Wenyang
AU  - Li W
AUID- ORCID: 0000-0001-6495-6966
AD  - Department of Neurosurgery, The Second Xiangya Hospital of Central South 
      University, Changsha, China.
FAU - Wang, Ming
AU  - Wang M
AUID- ORCID: 0000-0001-6772-8299
AD  - Department of Neurosurgery, The Second Xiangya Hospital of Central South 
      University, Changsha, China.
FAU - Ma, Wenjia
AU  - Ma W
AD  - Department of Neurosurgery, The Second Xiangya Hospital of Central South 
      University, Changsha, China.
FAU - Liu, Ping
AU  - Liu P
AD  - Department of Oncology, The Second Xiangya Hospital of Central South University, 
      Changsha, China.
FAU - Zhang, Mingming
AU  - Zhang M
AD  - Department of Neurosurgery, The Second Xiangya Hospital of Central South 
      University, Changsha, China.
FAU - He, Jiarong
AU  - He J
AD  - Department of Neurosurgery, The Second Xiangya Hospital of Central South 
      University, Changsha, China.
FAU - Cui, Yan
AU  - Cui Y
AUID- ORCID: 0000-0003-1234-222X
AD  - Department of Neurosurgery, The Second Xiangya Hospital of Central South 
      University, Changsha, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230329
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (EGR2 protein, human)
RN  - 0 (SOX4 protein, human)
RN  - 0 (SOXC Transcription Factors)
RN  - YF1K15M17Y (Temozolomide)
RN  - 0 (Transcription Factors)
RN  - 0 (RNA, Long Noncoding)
SB  - IM
EIN - CNS Neurosci Ther. 2023 Jun 22;:. PMID: 37349972
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Down-Regulation
MH  - *Early Growth Response Protein 2/genetics/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - *Glioblastoma/genetics
MH  - Mice, Nude
MH  - *SOXC Transcription Factors/genetics/metabolism
MH  - Temozolomide/pharmacology
MH  - Transcription Factors/genetics
MH  - *RNA, Long Noncoding/genetics
PMC - PMC10352878
OTO - NOTNLM
OT  - LINC00470
OT  - SRY-related high-mobility-group box 4
OT  - angiogenesis
OT  - apoptosis
OT  - autophagy
OT  - early growth response 2
OT  - glioblastoma
OT  - temozolomide
COIS- The authors declare that they have no competing interests.
EDAT- 2023/03/30 06:00
MHDA- 2023/07/19 06:43
PMCR- 2023/03/29
CRDT- 2023/03/29 03:23
PHST- 2023/02/17 00:00 [revised]
PHST- 2022/08/11 00:00 [received]
PHST- 2023/03/05 00:00 [accepted]
PHST- 2023/07/19 06:43 [medline]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/29 03:23 [entrez]
PHST- 2023/03/29 00:00 [pmc-release]
AID - CNS14181 [pii]
AID - 10.1111/cns.14181 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2023 Aug;29(8):2292-2307. doi: 10.1111/cns.14181. Epub 2023 
      Mar 29.