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circELMOD3 increases and stabilizes TRIM13 by sponging miR-6864-5p and direct binding to inhibit HCC progression
Mingshuang Lai1,2, Meiliang Liu1,2, Deyuan Li1,2
1School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China.
Abstract:
Many circular RNAs (circRNAs) have been identified to be associated with hepatocellular carcinoma (HCC) progression. We aim to explore the diagnostic potential, functions, and mechanism of circELMOD3 in HCC. Differentially expressed circRNAs in HCC and its paired adjacent tissues were identified by RNA sequencing. circELMOD3 was downregulated in HCC tissues and was related to clinicopathological characteristics of HCC patients. Additionally, plasma circELMOD3 was shown to be a highly sensitive and non-invasive biomarker to distinguish HCC from healthy controls. Functional assays showed that circELMOD3 inhibited proliferation and induced apoptosis of HCC cells both in vitro and in vivo. Mechanistically, RNA antisense purification (RAP) and luciferase reporter assays verified that circELMOD3 functioned as a sponge for miR-6864-5p leading to increased expression of its target gene TRIM13. Interestingly, RNA stability test demonstrated that circELMOD3 overexpression led to enhanced stability of its directly bound TRIM13 mRNA, which in turn co-activated the p53 signaling pathway.
Insights
Circular RNA ELMOD3 (circELMOD3) is downregulated in hepatocellular carcinoma (HCC) and serves as a promising diagnostic biomarker. circELMOD3 inhibits tumor growth and promotes apoptosis by regulating the miR-6864-5p/TRIM13/p53 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Circular RNAs (circRNAs) are increasingly implicated in hepatocellular carcinoma (HCC) pathogenesis.
- Understanding the role of specific circRNAs, like circELMOD3, is crucial for HCC diagnosis and treatment.
Purpose of the Study:
- To investigate the diagnostic value, functional roles, and underlying mechanisms of circELMOD3 in hepatocellular carcinoma.
- To explore circELMOD3 as a potential non-invasive biomarker for HCC detection.
Main Methods:
- RNA sequencing to identify differentially expressed circRNAs in HCC tissues.
- Quantitative real-time PCR and plasma assays for circELMOD3 detection.
- In vitro and in vivo functional assays to assess proliferation and apoptosis.
- RNA antisense purification (RAP) and luciferase reporter assays to elucidate molecular mechanisms.
Main Results:
- circELMOD3 was significantly downregulated in HCC tissues and correlated with clinicopathological features.
- Plasma circELMOD3 demonstrated high sensitivity and specificity as a biomarker for distinguishing HCC from healthy controls.
- circELMOD3 overexpression suppressed HCC cell proliferation and induced apoptosis both in vitro and in vivo.
- circELMOD3 acts as a molecular sponge for miR-6864-5p, upregulating TRIM13 expression and stabilizing its mRNA.
- circELMOD3, via TRIM13, co-activates the p53 signaling pathway.
Conclusions:
- circELMOD3 is a potential non-invasive diagnostic biomarker for HCC.
- circELMOD3 functions as a tumor suppressor in HCC by inhibiting proliferation and inducing apoptosis.
- The circELMOD3/miR-6864-5p/TRIM13/p53 axis represents a novel therapeutic target for HCC.
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