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The reciprocal regulation loop of Notch2 pathway and miR-23b in controlling gastric carcinogenesis
- Source :
- Oncotarget
- Publication Year :
- 2015
-
Abstract
- Gastric carcinoma is one of the most common malignancies and the third highest cause of global cancer-related death. Notch2 receptor intracellular domain (N2IC), the activated form of Notch2 receptor, enhances gastric carcinogenesis. MicroRNAs (miRNAs) act as either oncogenes or tumor suppressors in tumorigenesis and cross-talk with Notch pathways. Herein, microRNA-23b (miR-23b) was identified as a Notch2 receptor-related miRNA and its role in gastric carcinogenesis was investigated. Levels of miR-23b in stomach adenocarcinoma samples were down-regulated, whereas those of Notch2 receptor, v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1), and E2F1 transcripts were up-regulated. Results also showed that N2IC down-regulated miR-23b expression in gastric cancer cells through up-regulating E2F1. The miR-23b inhibited gastric tumorigenesis including growth, viability, epithelial-mesenchymal transition, and abilities of colony formation, migration, invasion, and tumorsphere formation. Mechanistically, miR-23b suppressed tumor progression and pluripotency gene expression and affected tumorsphere ultra-structure in gastric cancer cells via targeting Notch2 receptor or Ets1. Furthermore, miR-23b diminished the xenografted tumor growth and lung metastasis of SC-M1 gastric cancer cells through Notch2 pathway. Our results suggest that Notch2 pathway and miR-23b interplay in a reciprocal regulation loop in gastric cancer cells and this axis plays an important role in gastric carcinogenesis.
- Subjects :
- Male
Pathology
Lung Neoplasms
Time Factors
Ets1
Mice, SCID
medicine.disease_cause
Cell Movement
Mice, Inbred NOD
Receptor, Notch2
3' Untranslated Regions
miR-23b
Mice, Inbred BALB C
notch2 receptor
Gene Expression Regulation, Neoplastic
Oncology
gastric carcinogenesis
Neoplastic Stem Cells
Adenocarcinoma
Signal transduction
Signal Transduction
Research Paper
Pluripotent Stem Cells
medicine.medical_specialty
endocrine system
Epithelial-Mesenchymal Transition
Mice, Nude
Transfection
Proto-Oncogene Protein c-ets-1
Stomach Neoplasms
Cell Line, Tumor
microRNA
medicine
Animals
Humans
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Cell Proliferation
Binding Sites
Oncogene
business.industry
Genetic Therapy
medicine.disease
Xenograft Model Antitumor Assays
MicroRNAs
E2F1
Tumor progression
Cancer cell
Cancer research
business
Carcinogenesis
E2F1 Transcription Factor
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 6
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....b57a76d71d28ababfae3d1e4f03e0f88