Long noncoding RNA ATB participates in the development of renal cell carcinoma by downregulating p53 via binding to
Chao Song1, Yunhe Xiong1, Wenbiao Liao1
1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
Abstract:
Long noncoding RNA (lncRNA) exerts an essential role in the pathological processes of many diseases. Our previous study found that lncRNA ATB was highly expressed in renal cell carcinoma (RCC). Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and migration-related assays were conducted to access the regulatory effects of lncRNA ATB on proliferative and migratory capacities of RCC cells. Flow cytometry was carried out to determine cell cycle and apoptosis influenced by lncRNA ATB. The interaction among lncRNA ATB, DNMT1, and p53 was evaluated through RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and western blot analyses. The results showed that lncRNA ATB knockdown in RCC cell line ACHN inhibited proliferative and migratory capacities and promoted apoptosis. Meanwhile, overexpression of lncRNA ATB in RCC cell line A-498 promoted proliferative and migratory capacities but inhibited apoptosis. RIP and ChIP assays confirmed that lncRNA ATB can bind to DNMT1 and stabilize its expression; meanwhile, it can promote the binding of DNMT1 to p53. Overexpression of p53 partially reversed the proliferative and migratory changes caused by lncRNA ATB. To sum up, our study revealed that high expression of lncRNA ATB could accelerate the proliferative and migratory rates of RCC cells and inhibit cell apoptosis through downregulating p53 via binding to DNMT1.
Insights
Long noncoding RNA ATB promotes renal cell carcinoma (RCC) progression by enhancing cell proliferation and migration while inhibiting apoptosis. It achieves this by binding to DNMT1, which then downregulates p53 expression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are implicated in various disease pathologies.
- Aberrant expression of lncRNA ATB has been observed in renal cell carcinoma (RCC).
Purpose of the Study:
- To investigate the role of lncRNA ATB in regulating the proliferative and migratory capacities of RCC cells.
- To elucidate the molecular mechanism by which lncRNA ATB influences RCC cell cycle and apoptosis.
- To examine the interaction between lncRNA ATB, DNMT1, and p53 in RCC.
Main Methods:
- Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and migration assays were used to assess cellular functions.
- Flow cytometry was employed to analyze cell cycle and apoptosis.
- RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and western blot analyses were performed to study molecular interactions.
Main Results:
- lncRNA ATB knockdown inhibited proliferation and migration, and promoted apoptosis in RCC cells.
- lncRNA ATB overexpression enhanced proliferation and migration, and inhibited apoptosis in RCC cells.
- lncRNA ATB binds to DNMT1, stabilizing its expression and promoting DNMT1-p53 binding, ultimately downregulating p53.
Conclusions:
- High expression of lncRNA ATB accelerates proliferation and migration while inhibiting apoptosis in RCC cells.
- lncRNA ATB exerts its oncogenic effects by downregulating p53 through interaction with DNMT1.
- Targeting lncRNA ATB may represent a potential therapeutic strategy for renal cell carcinoma.
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