PMID- 34396632
OWN - NLM
STAT- MEDLINE
DCOM- 20211112
LR  - 20220531
IS  - 1523-5378 (Electronic)
IS  - 1083-4389 (Linking)
VI  - 26
IP  - 6
DP  - 2021 Dec
TI  - Long noncoding RNA NEAT1 promotes tumorigenesis in H. pylori gastric cancer by 
      sponging miR-30a to regulate COX-2/BCL9 pathway.
PG  - e12847
LID - 10.1111/hel.12847 [doi]
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is a carcinogenic factor for gastric 
      cancer. Our previous study demonstrated that H. pylori decreased the expression 
      of micro-RNA (miRNA)-30a to promote the tumorigenesis of gastric cancer. However, 
      the upstream regulatory molecules of miR-30a are not well elucidated. In this 
      study, we found the long non-coding RNA (lncRNA) nuclear paraspeckle assembly 
      transcript 1 (NEAT1) may sponge miR-30a to regulate COX-2/BCL9 pathway. METHODS: 
      The expression of NEAT1 was detected in gastric cancer tissues and tumor-adjacent 
      tissues by fluorescence in situ hybridization (FISH) analysis and RT-qPCR. 
      LncRNA-miRNA interaction networks were constructed using the RNAhybrid and 
      starBase v.2.0. and then validated using a dual-luciferase reporter assay. The 
      effects of NEAT1 dysregulation on the proliferative, migratory, and invasive 
      abilities of H. pylori filtrate-infected gastric cancer cells were observed by 
      cell counting kit-8 (CCK-8), colony formation, wound healing test, and transwell 
      assays. Western blot and RT-qPCR were performed to detect protein and RNA 
      expression. Immunohistochemistry (IHC) was carried out to analyze the 
      localization and expression of COX-2 and BCL9. RESULTS: FISH and RT-qPCR 
      demonstrated that the expression of NEAT1 was up-regulated in gastric cancer 
      tissues, especially in H. pylori-infected gastric cancer tissues, and the 
      expression of NEAT1 was negatively correlated with miR-30a (miR-30a-3p and 
      miR-30a-5p). The upregulation of NEAT1 enhanced proliferation, migration, and 
      invasion of H. pylori filtrate-infected gastric cancer cells, while the 
      downregulation of NEAT1 decreased these abilities, and miR-30a could reverse the 
      effect of NEAT1 on these abilities. The dual-luciferase reporter assay identified 
      that NEAT1 directly targeted miR-30a (miR-30a-3p and miR-30a-5p). Because miR-30a 
      (miR-30a-3p and miR-30a-5p) negatively regulates the expression of downstream 
      COX-2 and BCL9, NEAT1 was identified to upregulate indirectly the expression of 
      COX-2 and BCL9. IHC showed that the expression of COX-2 and BCL9 was increased in 
      H. pylori gastric cancer tissues. CONCLUSION: The study demonstrated that lncRNA 
      NEAT1 may act as a promoter of tumorigenesis in H. pylori gastric cancer, by 
      sponging miR-30a (miR-30a-3p and miR-30a-5p) to regulate the COX-2/BCL9 pathway.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Rao, Xiwu
AU  - Rao X
AD  - Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Liu, Xuan
AU  - Liu X
AD  - Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Liu, Ningning
AU  - Liu N
AD  - Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Zhang, Zhaozhou
AU  - Zhang Z
AD  - Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Zhou, Lihong
AU  - Zhou L
AD  - Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Han, Gang
AU  - Han G
AD  - Department of Gastrointestinal Surgery, Shuguang Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Cen, Rong
AU  - Cen R
AD  - Department of Gastroenterology, Shuguang Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Shi, Nuolin
AU  - Shi N
AD  - Academy of Integrative Medicine, Shanghai University of Traditional Chinese 
      Medicine, Shanghai, China.
FAU - Zhu, Huirong
AU  - Zhu H
AD  - Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Gong, Hangjun
AU  - Gong H
AD  - Department of Gastrointestinal Surgery, Shuguang Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Huang, Chen
AU  - Huang C
AD  - Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
FAU - Ji, Qing
AU  - Ji Q
AD  - Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Li, Qi
AU  - Li Q
AUID- ORCID: 0000-0003-2004-6885
AD  - Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
AD  - Academy of Integrative Medicine, Shanghai University of Traditional Chinese 
      Medicine, Shanghai, China.
LA  - eng
GR  - 81874405/National Natural Science Foundation of China/
GR  - 19ZR1458500/Natural Science Foundation of Shanghai/
PT  - Journal Article
DEP - 20210816
PL  - England
TA  - Helicobacter
JT  - Helicobacter
JID - 9605411
RN  - 0 (BCL9 protein, human)
RN  - 0 (MIRN30a microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NEAT1 long non-coding RNA, human)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Transcription Factors)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Carcinogenesis/genetics
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - *Cyclooxygenase 2/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - *Helicobacter Infections/complications/genetics
MH  - Helicobacter pylori
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *MicroRNAs/genetics
MH  - *RNA, Long Noncoding/genetics
MH  - *Stomach Neoplasms/genetics/microbiology
MH  - *Transcription Factors/genetics
OTO - NOTNLM
OT  - H. pylori
OT  - NEAT1
OT  - COX-2/BCL9 pathway
OT  - gastric cancer
OT  - miR-30a
EDAT- 2021/08/17 06:00
MHDA- 2021/11/16 06:00
CRDT- 2021/08/16 06:25
PHST- 2021/07/31 00:00 [revised]
PHST- 2021/06/17 00:00 [received]
PHST- 2021/08/03 00:00 [accepted]
PHST- 2021/08/17 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2021/08/16 06:25 [entrez]
AID - 10.1111/hel.12847 [doi]
PST - ppublish
SO  - Helicobacter. 2021 Dec;26(6):e12847. doi: 10.1111/hel.12847. Epub 2021 Aug 16.