PMID- 33568625
OWN - NLM
STAT- MEDLINE
DCOM- 20210914
LR  - 20240226
IS  - 2041-4889 (Electronic)
VI  - 12
IP  - 2
DP  - 2021 Feb 10
TI  - circST6GALNAC6 suppresses bladder cancer metastasis by sponging miR-200a-3p to 
      modulate the STMN1/EMT axis.
PG  - 168
LID - 10.1038/s41419-021-03459-4 [doi]
LID - 168
AB  - Bladder cancer (BCa) is an aggressive malignancy because of its distant 
      metastasis and high recurrence rate. Circular RNAs (circRNAs) exert critical 
      regulatory functions in cancer progression. However, the expression patterns and 
      roles of circRNAs in BCa have not been well investigated. In this study, we first 
      screened circRNA expression profiles using a circRNA microarray of paired BCa and 
      normal tissues, and the expression of circST6GALNAC6 was confirmed by qRT-PCR and 
      fluorescence in situ hybridization (FISH). MTT, colony formation and Transwell 
      assays were performed to measure cell proliferation, migration and invasion. We 
      investigated the regulatory effect of circST6GALNAC6 on miRNA and its target 
      genes to explore the potential regulatory mechanisms of circST6GALNAC6 by 
      chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), MS2-tagged 
      RNA affinity purification (MS2-TRAP), immunofluorescence (IF) and dual luciferase 
      activity assays. A nude mouse xenograft model was used to examine the functions 
      of circST6GALNAC6/STMN1 in tumour metastasis in vivo. We found that 881 circRNAs 
      were significantly dysregulated in BCa tissues compared to normal tissues. 
      circST6GALNAC6(hsa_circ_0088708) was downregulated in BCa tissues and cells. 
      Overexpression of circST6GALNAC6 effectively inhibited the cell proliferation, 
      migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and 
      suppressed BCa metastasis in vivo. Mechanistically, we showed that the SP1 
      transcription factor, which binds to the circST6GALNAC6 mRNA transcript, 
      activates circST6GALNAC6 transcription. Next, we verified that circST6GALNAC6 
      serves as a sponge that directly binds miR-200a-3p to regulate stathmin (STMN1) 
      expression. Furthermore, we found that STMN1 is involved in 
      circST6GALNAC6/miR-200a-3p axis-regulated BCa EMT and metastasis. Thus, our 
      findings indicate an important underlying mechanism in BCa metastasis by which 
      SP1-induced circST6GALNAC6 sponges miR-200a-3p to promote STMN1/EMT signalling. 
      This mechanism could provide pivotal potential prognostic biomarkers and 
      therapeutic targets for BCa.
FAU - Tan, Shuo
AU  - Tan S
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
AD  - Department of Urology, Xiangya Hospital, Central South University, Changsha, 
      Hunan Province, P R China.
FAU - Kang, Ye
AU  - Kang Y
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
FAU - Li, Hu
AU  - Li H
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
FAU - He, Hai-Qing
AU  - He HQ
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
FAU - Zheng, Long
AU  - Zheng L
AD  - Department of Urology, An Xiang Xian People's Hospital, Anxiang, Hunan Province, 
      P R China.
FAU - Wu, Shui-Qing
AU  - Wu SQ
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
FAU - Ai, Kai
AU  - Ai K
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
FAU - Xu, Ran
AU  - Xu R
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
FAU - Zhang, Xuan-Zhi
AU  - Zhang XZ
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
FAU - Zhao, Xiao-Kun
AU  - Zhao XK
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China.
FAU - Zhu, Xuan
AU  - Zhu X
AD  - Department of Urology, the Second Xiangya Hospital of Central South University, 
      Changsha, Hunan Province, P R China. zhuxuan@csu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210210
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (MIRN200 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - 0 (STMN1 protein, human)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (SP1 protein, human)
RN  - 0 (Stathmin)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - *Cell Movement
MH  - Cell Proliferation
MH  - *Epithelial-Mesenchymal Transition
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice, Nude
MH  - MicroRNAs/genetics/*metabolism
MH  - Neoplasm Invasiveness
MH  - RNA, Circular/genetics/*metabolism
MH  - Signal Transduction
MH  - Sp1 Transcription Factor/genetics/metabolism
MH  - Stathmin/genetics/*metabolism
MH  - Urinary Bladder Neoplasms/genetics/*metabolism/pathology
MH  - Mice
PMC - PMC7876104
COIS- The authors declare no competing interests.
EDAT- 2021/02/12 06:00
MHDA- 2021/09/15 06:00
PMCR- 2021/02/10
CRDT- 2021/02/11 05:46
PHST- 2020/08/25 00:00 [received]
PHST- 2021/01/21 00:00 [accepted]
PHST- 2021/01/14 00:00 [revised]
PHST- 2021/02/11 05:46 [entrez]
PHST- 2021/02/12 06:00 [pubmed]
PHST- 2021/09/15 06:00 [medline]
PHST- 2021/02/10 00:00 [pmc-release]
AID - 10.1038/s41419-021-03459-4 [pii]
AID - 3459 [pii]
AID - 10.1038/s41419-021-03459-4 [doi]
PST - epublish
SO  - Cell Death Dis. 2021 Feb 10;12(2):168. doi: 10.1038/s41419-021-03459-4.