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23 January 2019 : Clinical Research  

Long Noncoding RNA (lncRNA) MIR22HG Suppresses Gastric Cancer Progression through Attenuating NOTCH2 Signaling

Huihui Li1AB*, Yue Wang2BC

DOI: 10.12659/MSM.912813

Med Sci Monit 2019; 25:656-665

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.

Keywords: Receptor, Notch2, RNA, Long Noncoding, Stomach Neoplasms, Apoptosis, China, Disease Progression, Gene Expression Regulation, Neoplastic, Kaplan-Meier Estimate, MicroRNAs, Middle Aged, Neoplasm Invasiveness, Prognosis, Survival Rate

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750