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Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma
Jian Yu1, Qing-Guo Xu1, Zhen-Guang Wang1
1The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Background & Aims:
In recent years, circular RNAs (circRNAs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of circRNAs to hepatocellular carcinoma (HCC) remain largely unknown.
Methods:
cSMARCA5 (a circRNA derived from exons 15 and 16 of the SMARCA5 gene, hsa_circ_0001445) was identified by RNA-sequencing and validated by quantitative reverse transcription PCR. The role of cSMARCA5 in HCC progression was assessed both in vitro and in vivo. circRNAs in vivo precipitation, luciferase reporter assay, biotin-coupled microRNA capture and fluorescence in situ hybridization were conducted to evaluate the interaction between cSMARCA5 and miR-17-3p/miR-181b-5p.
Results:
The expression of cSMARCA5 was lower in HCC tissues, because of the regulation of DExH-Box Helicase 9, an abundant nuclear RNA helicase. The downregulation of cSMARCA5 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival and recurrence-free survival in patients with HCC after hepatectomy. Our in vivo and in vitro data indicated that cSMARCA5 inhibits the proliferation and migration of HCC cells. Mechanistically, we found that cSMARCA5 could promote the expression of TIMP3, a well-known tumor suppressor, by sponging miR-17-3p and miR-181b-5p.
Conclusion:
These results reveal an important role of cSMARCA5 in the growth and metastasis of HCC and provide a fresh perspective on circRNAs in HCC progression.
Lay Summary:
Herein, we studied the role of cSMARCA5, a circular RNA, in hepatocellular carcinoma. Our in vitro and in vivo data showed that cSMARCA5 inhibits the growth and migration of hepatocellular carcinoma cells, making it a potential therapeutic target.
Insights
Circular RNAs (circRNAs) like cSMARCA5 play a key role in hepatocellular carcinoma (HCC). Lower cSMARCA5 levels correlate with aggressive HCC, and it inhibits tumor growth and migration, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their regulatory roles in cancer biology.
- The specific involvement of circRNAs in hepatocellular carcinoma (HCC) pathogenesis remains largely underexplored.
Purpose of the Study:
- To investigate the role and mechanism of cSMARCA5, a specific circRNA, in the progression of hepatocellular carcinoma (HCC).
- To assess cSMARCA5 as a potential biomarker and therapeutic target for HCC.
Main Methods:
- Identification and validation of cSMARCA5 using RNA-sequencing and quantitative reverse transcription PCR.
- In vitro and in vivo experiments to evaluate cSMARCA5's effect on HCC cell proliferation and migration.
- Molecular assays including RNA immunoprecipitation, luciferase reporter assays, and fluorescence in situ hybridization to elucidate the interaction network of cSMARCA5 with microRNAs (miR-17-3p/miR-181b-5p) and target genes (TIMP3).
Main Results:
- cSMARCA5 expression was found to be downregulated in HCC tissues, correlated with advanced tumor characteristics and poorer patient survival outcomes.
- Downregulation of cSMARCA5 was linked to the regulation by DExH-Box Helicase 9.
- Experimental data demonstrated that cSMARCA5 inhibits HCC cell proliferation and migration.
- Mechanistically, cSMARCA5 acts as a sponge for miR-17-3p and miR-181b-5p, leading to the promotion of the tumor suppressor TIMP3 expression.
Conclusions:
- cSMARCA5 plays a significant inhibitory role in the growth and metastasis of hepatocellular carcinoma.
- The findings highlight cSMARCA5 as a potential diagnostic marker and therapeutic target for HCC, offering new insights into circRNA functions in cancer progression.
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