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Published on: December 1, 2023
Long Noncoding RNA (lncRNA) MIR22HG Suppresses Gastric Cancer Progression through Attenuating NOTCH2 Signaling
1Department of Digestive System, Beilun People's Hospital, Ningbo, Zhejiang, China (mainland).
Abstract:
BACKGROUND Long noncoding RNAs (lncRNAs) are important regulators in human disease, including cancers. LncRNA MIR22HG has been shown to inhibit the progression of endometrial carcinoma, lung cancer, and hepatocellular carcinoma. Its role in gastric cancer is unclear. This study investigated MIR22HG effects on gastric cancer. MATERIAL AND METHODS Gastric cancer tissues (n=43) and adjacent normal tissues (n=21) were collected. Patients' 5-year overall survival rate was analyzed. Human normal gastric mucosal cell line (GES-1) and gastric cancer cell lines (MKN-45, AGS, SGC-7901) were cultured. AGS and MKN-45 cells were transfected by pcDNA3 empty vector, pcDNA3-MIR22HG overexpression vector, MIR22HG siRNA and its negative control, NOTCH2 siRNA and its negative control, respectively. Proliferation was explored by CCK-8 assay. Migration and invasion were explored by Transwell. qRT-PCR and western blot were used to investigate mRNA and proteins expression, respectively. RESULTS MIR22HG expression was decreased in gastric cancer tissues and cells (P<0.05). Low MIR22HG expression indicated lower 5-year overall survival rate (P<0.05). Upregulation of MIR22HG inhibited AGS and MKN-45 cell proliferation, migration and invasion (all P<0.05). Downregulation of MIR22HG elevated AGS and MKN-45 cell proliferation, migration, and invasion (all P<0.05). MIR22HG negatively regulated NOTCH2 signaling. Silencing MIR22HG elevated HEY1 and nucleus NOTCH2 expression. Silencing of NOTCH2 suppressed AGS and MKN-45 cells proliferation, migration and invasion (all P<0.05). CONCLUSIONS LncRNA MIR22HG suppressed gastric cancer progression through attenuating NOTCH2 signaling.
Insights
Long noncoding RNA MIR22HG suppresses gastric cancer progression. Low MIR22HG levels correlate with reduced survival, and its upregulation inhibits tumor growth and spread by attenuating NOTCH2 signaling.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are key regulators in human diseases, including cancers.
- LncRNA MIR22HG is known to inhibit progression in endometrial carcinoma, lung cancer, and hepatocellular carcinoma.
- The specific role of MIR22HG in gastric cancer remains largely uncharacterized.
Purpose of the Study:
- To investigate the functional role of lncRNA MIR22HG in gastric cancer.
- To determine the relationship between MIR22HG expression and patient survival.
- To elucidate the molecular mechanism underlying MIR22HG's effect on gastric cancer progression, particularly its interaction with NOTCH2 signaling.
Main Methods:
- Analysis of MIR22HG expression in 43 gastric cancer tissues and 21 adjacent normal tissues.
- Correlation of MIR22HG expression with 5-year overall survival rates.
- In vitro studies using gastric cancer cell lines (AGS, MKN-45) involving overexpression and knockdown of MIR22HG and NOTCH2.
- Assessment of cell proliferation (CCK-8 assay), migration, and invasion (Transwell assay).
- Gene and protein expression analysis using qRT-PCR and Western blot.
Main Results:
- MIR22HG expression was significantly decreased in gastric cancer tissues and cells compared to normal controls.
- Lower MIR22HG expression was associated with a significantly lower 5-year overall survival rate.
- MIR22HG upregulation inhibited proliferation, migration, and invasion in gastric cancer cells, while its downregulation promoted these processes.
- MIR22HG negatively regulated NOTCH2 signaling, with MIR22HG silencing increasing HEY1 and nuclear NOTCH2 expression.
- NOTCH2 silencing suppressed the proliferation, migration, and invasion of gastric cancer cells.
Conclusions:
- LncRNA MIR22HG acts as a tumor suppressor in gastric cancer.
- MIR22HG suppresses gastric cancer progression by attenuating the NOTCH2 signaling pathway.
- MIR22HG may serve as a potential prognostic biomarker and therapeutic target for gastric cancer.
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