PMID- 36293387
OWN - NLM
STAT- MEDLINE
DCOM- 20221028
LR  - 20221030
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 20
DP  - 2022 Oct 19
TI  - SOX2 Promotes Invasion in Human Bladder Cancers through MMP2 Upregulation and 
      FOXO1 Downregulation.
LID - 10.3390/ijms232012532 [doi]
LID - 12532
AB  - SOX2, a member of the SRY-related HMG-box (SOX) family, is abnormally expressed 
      in many tumors and associated with cancer stem cell-like properties. Previous 
      reports have shown that SOX2 is a biomarker for cancer stem cells in human 
      bladder cancer (BC), and our most recent study has indicated that the inhibition 
      of SOX2 by anticancer compound ChlA-F attenuates human BC cell invasion. We now 
      investigated the mechanisms through which SOX2 promotes the invasive ability of 
      BC cells. Our studies revealed that SOX2 promoted SKP2 transcription and 
      increased SKP2-accelerated Sp1 protein degradation. As Sp1 is a transcriptionally 
      regulated gene, HUR transcription was thereby attenuated, and, in the absence of 
      HUR, FOXO1 mRNA was degraded fast, which promoted BC cell invasion. In addition, 
      SOX2 promoted BC invasion through the upregulation of nucleolin transcription, 
      which resulted in increased MMP2 mRNA stability and expression. Collectively, our 
      findings show that SOX2 promotes BC invasion through both SKP2-Sp1-HUR-FOXO1 and 
      nucleolin-MMP2 dual axes.
FAU - Xie, Qipeng
AU  - Xie Q
AUID- ORCID: 0000-0002-3292-2988
AD  - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain 
      Health), School of Laboratory Medicine and Life Sciences, Wenzhou Medical 
      University, Wenzhou 325000, China.
AD  - Department of Clinical Laboratory, The Second Affiliated Hospital & Yuying 
      Children's Hospital of Wenzhou Medical University, Wenzhou 325035, China.
FAU - Hua, Xiaohui
AU  - Hua X
AD  - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain 
      Health), School of Laboratory Medicine and Life Sciences, Wenzhou Medical 
      University, Wenzhou 325000, China.
FAU - Huang, Chao
AU  - Huang C
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Liao, Xin
AU  - Liao X
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Tian, Zhongxian
AU  - Tian Z
AD  - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain 
      Health), School of Laboratory Medicine and Life Sciences, Wenzhou Medical 
      University, Wenzhou 325000, China.
FAU - Xu, Jiheng
AU  - Xu J
AD  - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain 
      Health), School of Laboratory Medicine and Life Sciences, Wenzhou Medical 
      University, Wenzhou 325000, China.
FAU - Zhao, Yunping
AU  - Zhao Y
AD  - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain 
      Health), School of Laboratory Medicine and Life Sciences, Wenzhou Medical 
      University, Wenzhou 325000, China.
FAU - Jiang, Guosong
AU  - Jiang G
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Huang, Haishan
AU  - Huang H
AD  - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain 
      Health), School of Laboratory Medicine and Life Sciences, Wenzhou Medical 
      University, Wenzhou 325000, China.
FAU - Huang, Chuanshu
AU  - Huang C
AD  - Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain 
      Health), School of Laboratory Medicine and Life Sciences, Wenzhou Medical 
      University, Wenzhou 325000, China.
LA  - eng
GR  - NSFC81773391/National Natural Science Foundation of China/
GR  - OJQD2022006/Oujiang Research Project/
PT  - Journal Article
DEP - 20221019
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - 0 (MicroRNAs)
RN  - 0 (Biomarkers)
RN  - 0 (RNA, Messenger)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (SOX2 protein, human)
RN  - 0 (SOXB1 Transcription Factors)
RN  - EC 3.4.24.24 (MMP2 protein, human)
SB  - IM
MH  - Humans
MH  - Down-Regulation
MH  - Up-Regulation
MH  - *Urinary Bladder Neoplasms/metabolism
MH  - Matrix Metalloproteinase 2/genetics/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - *MicroRNAs/genetics
MH  - Cell Line, Tumor
MH  - Biomarkers
MH  - RNA, Messenger/genetics
MH  - Neoplasm Invasiveness/pathology
MH  - Forkhead Box Protein O1/genetics/metabolism
MH  - SOXB1 Transcription Factors/genetics/metabolism
PMC - PMC9604292
OTO - NOTNLM
OT  - FOXO1
OT  - SKP2
OT  - SOX2
OT  - bladder cancer invasion
OT  - nucleolin
COIS- Neither this paper nor any similar paper has been or will be submitted to or 
      published in any other scientific journal. All authors are aware and agree to the 
      content of the paper and to their being listed as an author on the manuscript. 
      There is no conflict of interest or competing financial interest for all authors.
EDAT- 2022/10/28 06:00
MHDA- 2022/10/29 06:00
PMCR- 2022/10/19
CRDT- 2022/10/27 01:24
PHST- 2022/09/05 00:00 [received]
PHST- 2022/10/03 00:00 [revised]
PHST- 2022/10/11 00:00 [accepted]
PHST- 2022/10/27 01:24 [entrez]
PHST- 2022/10/28 06:00 [pubmed]
PHST- 2022/10/29 06:00 [medline]
PHST- 2022/10/19 00:00 [pmc-release]
AID - ijms232012532 [pii]
AID - ijms-23-12532 [pii]
AID - 10.3390/ijms232012532 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Oct 19;23(20):12532. doi: 10.3390/ijms232012532.