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Published on: September 29, 2020
Circular RNA profiling identifies circADAMTS13 as a miR-484 sponge which suppresses cell proliferation in
Liman Qiu1,2, Yanbing Huang1,2,3, Zhenli Li1,2
1The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
Abstract:
Circular RNA (circRNA) can participate in various biological processes, including tumorigenesis, through their microRNA response elements. Alterations in circRNA profiles during hepatocellular carcinoma (HCC) progression and their clinical significance remain unclear. Here, we present extensive analysis of circRNA profiles in tumor and matched peritumor tissues collected from 10 HCC patients, conducted to identify circRNA related to HCC progression. A total of 42 dysregulated circRNA (38 down-regulated and 4 up-regulated) were identified in HCC tumor tissues compared with matched peritumor tissues, revealing the heterogeneity of circRNA profiles in HCC. CircADAMTS13, derived from Exon 13-14 of the ADAMTS13 gene, was significantly downregulated in HCC tumor tissues. Furthermore, clinicopathological analysis revealed that up-regulation of circADAMTS13 was negatively associated with tumor size but positively associated with prognosis. In addition, overexpression of circADAMTS13 could markedly inhibit HCC cell proliferation in vitro. Bioinformatic analysis and luciferase reporter assays further revealed that circADAMTS13 directly interacts with microRNA (miR)-484. Rescue experiments showed that miR-484 mimics can reverse the tumor-suppressing roles of circADAMTS13 in HCC. Therefore, our results demonstrated that circADAMTS13 can serve as a tumor suppressor during HCC progression via the functional pathway of sponging miR-484.
Insights
Circular RNAs (circRNAs) are altered in hepatocellular carcinoma (HCC). CircADAMTS13 acts as a tumor suppressor by sponging miR-484, offering potential for HCC diagnosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) influence biological processes, including cancer development, via microRNA response elements.
- circRNA expression patterns and clinical relevance in hepatocellular carcinoma (HCC) progression are not fully understood.
Purpose of the Study:
- To identify circRNAs associated with HCC progression and elucidate their clinical significance.
- To investigate the role of circADAMTS13 in HCC development and its underlying molecular mechanism.
Main Methods:
- Comparative analysis of circRNA profiles in tumor and matched peritumor tissues from 10 HCC patients.
- Clinicopathological correlation, in vitro proliferation assays, bioinformatic analysis, and luciferase reporter assays.
- Rescue experiments to validate the interaction between circADAMTS13 and miR-484.
Main Results:
- Identified 42 dysregulated circRNAs in HCC tissues, highlighting significant heterogeneity.
- CircADAMTS13 was downregulated in HCC and its upregulation correlated with smaller tumor size and better prognosis.
- Overexpression of circADAMTS13 inhibited HCC cell proliferation, acting as a tumor suppressor by sponging miR-484.
Conclusions:
- CircADAMTS13 functions as a tumor suppressor in HCC progression.
- CircADAMTS13 may serve as a potential diagnostic biomarker and therapeutic target for HCC via the miR-484 pathway.
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