PMID- 33512745
OWN - NLM
STAT- MEDLINE
DCOM- 20220114
LR  - 20240226
IS  - 1878-0261 (Electronic)
IS  - 1574-7891 (Print)
IS  - 1574-7891 (Linking)
VI  - 15
IP  - 4
DP  - 2021 Apr
TI  - LncRNA NKX2-1-AS1 promotes tumor progression and angiogenesis via upregulation of 
      SERPINE1 expression and activation of the VEGFR-2 signaling pathway in gastric 
      cancer.
PG  - 1234-1255
LID - 10.1002/1878-0261.12911 [doi]
AB  - Long noncoding RNAs (lncRNAs) can compete with endogenous RNAs to modulate the 
      gene expression and contribute to oncogenesis and tumor metastasis. lncRNA 
      NKX2-1-AS1 (NKX2-1 antisense RNA 1) plays a pivotal role in cancer progression 
      and metastasis; however, the contribution of aberrant expression of NKX2-1-AS1 
      and the mechanism by which it functions as a competing endogenous RNA (ceRNA) in 
      gastric cancer (GC) remains elusive. NKX2-1-AS1 expression was detected in paired 
      tumor and nontumor tissues of 178 GC patients by quantitative reverse 
      transcription PCR (qRT-PCR). Using loss-of-function and gain-of-function 
      experiments, the biological functions of NKX2-1-AS1 were evaluated both in vitro 
      and in vivo. Further, to assess that NKX2-1-AS1 regulates angiogenic processes, 
      tube formation and co-culture assays were performed. RNA binding protein 
      immunoprecipitation (RIP) assay, a dual-luciferase reporter assay, quantitative 
      PCR, Western blot, and fluorescence in situ hybridization (FISH) assays were 
      performed to determine the potential molecular mechanism underlying this ceRNA. 
      The results indicated that NKX2-1-AS1 expression was upregulated in GC cell lines 
      and tumor tissues. Overexpression of NKX2-1-AS1 was significantly associated with 
      tumor progression and enhanced angiogenesis. Functionally, NKX2-1-AS1 
      overexpression promoted GC cell proliferation, metastasis, invasion, and 
      angiogenesis, while NKX2-1-AS1 knockdown restored these effects, both in vitro 
      and in vivo. RIP and dual-luciferase assays revealed that the microRNA miR-145-5p 
      is a direct target of NKX2-1-AS1 and that NKX2-1-AS1 serves as a ceRNA to sponge 
      miRNA and regulate angiogenesis in GC. Moreover, serpin family E member 1 
      (SERPINE1) is an explicit target for miR-145-5p; besides, the 
      NKX2-1-AS1/miR-145-5p axis induces the translation of SERPINE1, thus activating 
      the VEGFR-2 signaling pathway to promote tumor progression and angiogenesis. 
      NKX2-1-AS1 overexpression is associated with enhanced tumor cell proliferation, 
      angiogenesis, and poor prognosis in GC. Collectively, NKX2-1-AS1 functions as a 
      ceRNA to miR-145-5p and promotes tumor progression and angiogenesis by activating 
      the VEGFR-2 signaling pathway via SERPINE1.
CI  - (c) 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on 
      behalf of Federation of European Biochemical Societies.
FAU - Teng, Fei
AU  - Teng F
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
FAU - Zhang, Ju-Xiang
AU  - Zhang JX
AD  - Shanghai Med-X Engineering Center for Medical Equipment and Technology, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, China.
FAU - Chen, Yi
AU  - Chen Y
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
FAU - Shen, Xiao-Dong
AU  - Shen XD
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
FAU - Su, Chang
AU  - Su C
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
FAU - Guo, Yan-Jiao
AU  - Guo YJ
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
FAU - Wang, Pu-Hua
AU  - Wang PH
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
FAU - Shi, Chen-Cheng
AU  - Shi CC
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
FAU - Lei, Ming
AU  - Lei M
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
FAU - Cao, Yi-Ou
AU  - Cao YO
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
FAU - Liu, Shao-Qun
AU  - Liu SQ
AUID- ORCID: 0000-0002-2016-0947
AD  - Department of Gastrointestinal Surgery, Minhang Hospital, Fudan University, 
      Shanghai, China.
AD  - Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210213
PL  - United States
TA  - Mol Oncol
JT  - Molecular oncology
JID - 101308230
RN  - 0 (MIRN145 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (SERPINE1 protein, human)
RN  - EC 2.7.10.1 (KDR protein, human)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - MicroRNAs/genetics
MH  - Neovascularization, Pathologic
MH  - Plasminogen Activator Inhibitor 1/*genetics
MH  - RNA, Long Noncoding/*genetics
MH  - *Signal Transduction
MH  - Stomach Neoplasms/*pathology
MH  - Vascular Endothelial Growth Factor Receptor-2
MH  - Mice
PMC - PMC8024734
OTO - NOTNLM
OT  - NKX2-1 antisense RNA 1
OT  - VEGFR-2 signaling pathway
OT  - competing endogenous RNA
OT  - gastric cancer
OT  - serpin family E member 1
COIS- The authors declare no conflict of interest.
EDAT- 2021/01/30 06:00
MHDA- 2022/01/15 06:00
PMCR- 2021/04/01
CRDT- 2021/01/29 12:17
PHST- 2020/12/26 00:00 [revised]
PHST- 2020/09/16 00:00 [received]
PHST- 2021/01/05 00:00 [accepted]
PHST- 2021/01/30 06:00 [pubmed]
PHST- 2022/01/15 06:00 [medline]
PHST- 2021/01/29 12:17 [entrez]
PHST- 2021/04/01 00:00 [pmc-release]
AID - MOL212911 [pii]
AID - 10.1002/1878-0261.12911 [doi]
PST - ppublish
SO  - Mol Oncol. 2021 Apr;15(4):1234-1255. doi: 10.1002/1878-0261.12911. Epub 2021 Feb 
      13.