PMID- 30261900
OWN - NLM
STAT- MEDLINE
DCOM- 20190423
LR  - 20240331
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 17
IP  - 1
DP  - 2018 Sep 27
TI  - Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-beta-induced 
      epithelial-mesenchymal transition and metastasis by controlling TIF1gamma in 
      non-small cell lung cancer.
PG  - 140
LID - 10.1186/s12943-018-0889-7 [doi]
LID - 140
AB  - BACKGROUND: TGF-beta promotes tumor invasion and metastasis through inducing 
      epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). 
      Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in 
      human cancers. However, whether and how circRNAs contribute to TGF-beta-induced EMT 
      and metastasis in NSCLC remain vague. Here, we investigated the regulation and 
      function of Circular RNA hsa_circ_0008305 (circPTK2) in TGF-beta-induced EMT and 
      tumor metastasis, as well as a link between circPTK2 and transcriptional 
      intermediary factor 1 gamma (TIF1gamma) in NSCLC. METHODS: Circular RNAs were determined 
      by human circRNA Array analysis, real-time quantitative reverse transcriptase PCR 
      and northern blot. Luciferase reporter, RNA-binding protein immunoprecipitation 
      (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were 
      employed to test the interaction between circPTK2 and miR-429/miR-200b-3p. 
      Ectopic overexpression and siRNA-mediated knockdown of circPTK2, TGF-beta-induced 
      EMT, Transwell migration and invasion in vitro, and in vivo experiment of 
      metastasis were used to evaluate the function of circPTK2. Transcription and 
      prognosis analyses were done in public databases. RESULTS: CircPTK2 and TIF1gamma 
      were significantly down-regulated in NSCLC cells undergoing EMT induced by TGF-beta. 
      CircPTK2 overexpression augmented TIF1gamma expression, inhibited TGF-beta-induced EMT 
      and NSCLC cell invasion, whereas circPTK2 knockdown had the opposite effects. 
      CircPTK2 functions as a sponge of miR-429/miR-200b-3p, and miR-429/miR-200b-3p 
      promote TGF-beta-induced EMT and NSCLC cell invasion by targeting TIF1gamma. CircPTK2 
      overexpression inhibited the invasion-promoting phenotype of endogenous 
      miR-429/miR-200b-3p in NSCLC cells in response to TGF-beta. CircPTK2 overexpression 
      significantly decreased the expression of Snail, an important downstream 
      transcriptional activator of TGF-beta/Smad signaling. In an in vivo experiment of 
      metastasis, circPTK2 overexpression suppressed NSCLC cell metastasis. Moreover, 
      circPTK2 expression was dramatically down-regulated and positively correlated 
      with TIF1gamma expression in human NSCLC tissues. Especially, circPTK2 was 
      significantly lower in metastatic NSCLC tissues than non-metastatic counterparts. 
      CONCLUSION: Our findings show that circPTK2 (hsa_circ_0008305) inhibits 
      TGF-beta-induced EMT and metastasis by controlling TIF1gamma in NSCLC, revealing a novel 
      mechanism by which circRNA regulates TGF-beta-induced EMT and tumor metastasis, and 
      suggesting that circPTK2 overexpression could provide a therapeutic strategy for 
      advanced NSCLC.
FAU - Wang, Longqiang
AU  - Wang L
AD  - Soochow University Laboratory of Cancer Molecular Genetics, Medical College of 
      Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.
FAU - Tong, Xin
AU  - Tong X
AD  - Soochow University Laboratory of Cancer Molecular Genetics, Medical College of 
      Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.
FAU - Zhou, Zhengyu
AU  - Zhou Z
AD  - Soochow University Laboratory of Cancer Molecular Genetics, Medical College of 
      Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.
AD  - Laboratory Animal Center, Medical College of Soochow University, Suzhou, 215123, 
      Jiangsu, China.
FAU - Wang, Shengjie
AU  - Wang S
AD  - Soochow University Laboratory of Cancer Molecular Genetics, Medical College of 
      Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.
AD  - Department of Basic Medicine, Kangda College of Nanjing Medical University, 
      Lianyungang, 222000, China.
FAU - Lei, Zhe
AU  - Lei Z
AD  - Soochow University Laboratory of Cancer Molecular Genetics, Medical College of 
      Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.
FAU - Zhang, Tianze
AU  - Zhang T
AD  - Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical 
      University, 246 Xuefu Road, Harbin, 150086, Heilongjiang, China.
FAU - Liu, Zeyi
AU  - Liu Z
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Soochow 
      University, Medical College of Soochow University, Suzhou, 215006, Jiangsu, 
      China.
FAU - Zeng, Yuanyuan
AU  - Zeng Y
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Soochow 
      University, Medical College of Soochow University, Suzhou, 215006, Jiangsu, 
      China.
FAU - Li, Chang
AU  - Li C
AD  - Department of Thoracic Surgery, The First Affiliated Hospital of Soochow 
      University, Medical College of Soochow University, Suzhou, 215006, Jiangsu, 
      China.
FAU - Zhao, Jun
AU  - Zhao J
AD  - Department of Thoracic Surgery, The First Affiliated Hospital of Soochow 
      University, Medical College of Soochow University, Suzhou, 215006, Jiangsu, 
      China.
FAU - Su, Zhiyue
AU  - Su Z
AD  - Soochow University Laboratory of Cancer Molecular Genetics, Medical College of 
      Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.
FAU - Zhang, Cuijuan
AU  - Zhang C
AD  - Soochow University Laboratory of Cancer Molecular Genetics, Medical College of 
      Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.
FAU - Liu, Xia
AU  - Liu X
AD  - Soochow University Laboratory of Cancer Molecular Genetics, Medical College of 
      Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.
FAU - Xu, Guangquan
AU  - Xu G
AD  - Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical 
      University, 246 Xuefu Road, Harbin, 150086, Heilongjiang, China. 
      xvguangquanlb@163.com.
FAU - Zhang, Hong-Tao
AU  - Zhang HT
AUID- ORCID: 0000-0003-4182-421X
AD  - Soochow University Laboratory of Cancer Molecular Genetics, Medical College of 
      Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China. 
      htzhang@suda.edu.cn.
AD  - Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, 215123, Jiangsu, 
      China. htzhang@suda.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180927
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - 0 (TRIM33 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (PTK2 protein, human)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Biomarkers, Tumor
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/*pathology
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Epithelial-Mesenchymal Transition/drug effects/*genetics
MH  - Focal Adhesion Kinase 1/*genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Lung Neoplasms/*genetics/*pathology
MH  - MicroRNAs/genetics
MH  - Neoplasm Metastasis
MH  - *RNA
MH  - RNA Interference
MH  - RNA, Circular
MH  - Transcription Factors/*genetics
MH  - Transforming Growth Factor beta/pharmacology
PMC - PMC6161470
OTO - NOTNLM
OT  - CircPTK2
OT  - EMT
OT  - NSCLC
OT  - TIF1gamma
OT  - miR-429/miR-200b-3p
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was approved by the Ethics 
      Committee of Soochow University. CONSENT FOR PUBLICATION: Not applicable. 
      COMPETING INTERESTS: The authors declare that they have no competing interests. 
      PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional 
      claims in published maps and institutional affiliations.
EDAT- 2018/09/29 06:00
MHDA- 2019/04/24 06:00
PMCR- 2018/09/27
CRDT- 2018/09/29 06:00
PHST- 2018/03/22 00:00 [received]
PHST- 2018/09/13 00:00 [accepted]
PHST- 2018/09/29 06:00 [entrez]
PHST- 2018/09/29 06:00 [pubmed]
PHST- 2019/04/24 06:00 [medline]
PHST- 2018/09/27 00:00 [pmc-release]
AID - 10.1186/s12943-018-0889-7 [pii]
AID - 889 [pii]
AID - 10.1186/s12943-018-0889-7 [doi]
PST - epublish
SO  - Mol Cancer. 2018 Sep 27;17(1):140. doi: 10.1186/s12943-018-0889-7.