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Long Noncoding RNA ACTA2-AS1 Inhibits Cell Growth and Facilitates Apoptosis in Gastric Cancer by Binding with
Zuchao Hu1, Zhen Chen2, Wei Jiang2
1The Second Ward of Surgery, Sinophram Hanjiang Hospital, Shiyan, Hubei, China.
Abstract:
Gastric cancer (GC) is a common malignant tumor, posing a great threat to human's health and life. Previous studies have suggested aberrant expression of long non-coding RNAs (lncRNAs) in GC. This study elucidated the effects of lncRNA ACTA2-AS1 on the biological characteristics of GC. Gene expression in stomach adenocarcinoma (STAD) samples compared with normal tissues and the correlation between gene expression and prognosis of STAD patients were analyzed using bioinformatic tools. Gene expression at protein and mRNA levels in GC and normal cells was tested by western blotting and RT-qPCR. The subcellular localization of ACTA2-AS1 in AGS and HGC27 cells was identified by nuclear-cytoplasmic fractionation and FISH assay. EdU, CCK-8, flow cytometry analysis, TUNEL staining assays were conducted to evaluate the role of ACTA2-AS1 and ESRRB on GC cellular behaviors. The binding relationship among ACTA2-AS1, miR-6720-5p and ESRRB was verified by RNA pulldown, luciferase reporter assay and RIP assay. LncRNA ACTA2-AS1 was underexpressed in GC tissues and cell lines. ACTA2-AS1 elevation suppressed GC cell proliferation and induced apoptosis. Mechanistically, ACTA2-AS1 directly bound to miR-6720-5p and subsequently promoted the expression of target gene ESRRB in GC cells. Furthermore, ESRRB knockdown reversed the influence of ACTA2-AS1 overexpression on GC proliferation and apoptosis. ACTA2-AS1 plays an antioncogenic role in GC via binding with miR-6720-5p to regulate ESRRB expression.
Insights
Long non-coding RNA ACTA2-AS1 is underexpressed in gastric cancer (GC). Upregulating ACTA2-AS1 inhibits GC cell growth and promotes apoptosis by regulating the miR-6720-5p/ESRRB axis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) is a significant global health threat.
- Aberrant expression of long non-coding RNAs (lncRNAs) is implicated in GC development.
- The specific role of lncRNA ACTA2-AS1 in GC remains to be fully elucidated.
Purpose of the Study:
- To investigate the function and mechanism of lncRNA ACTA2-AS1 in gastric cancer.
- To analyze the correlation between ACTA2-AS1 expression and GC patient prognosis.
- To explore the regulatory network involving ACTA2-AS1, miR-6720-5p, and ESRRB in GC.
Main Methods:
- Bioinformatic analysis of GC and normal tissue gene expression and prognosis data.
- Western blotting and RT-qPCR to assess mRNA and protein levels.
- Cellular assays including EdU, CCK-8, flow cytometry, and TUNEL staining.
- Molecular assays such as nuclear-cytoplasmic fractionation, FISH, RNA pulldown, luciferase reporter assays, and RIP assay.
Main Results:
- LncRNA ACTA2-AS1 was found to be underexpressed in GC tissues and cell lines.
- Overexpression of ACTA2-AS1 suppressed GC cell proliferation and induced apoptosis.
- ACTA2-AS1 directly targets miR-6720-5p, leading to increased ESRRB expression.
- ESRRB knockdown reversed the anti-tumor effects of ACTA2-AS1 overexpression.
Conclusions:
- LncRNA ACTA2-AS1 functions as a tumor suppressor in gastric cancer.
- ACTA2-AS1 exerts its antioncogenic role by modulating the miR-6720-5p/ESRRB axis.
- ACTA2-AS1 may serve as a potential therapeutic target for gastric cancer treatment.
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