The Hsa_circ_0091579/miR-940/TACR1 Axis Regulates the Development of Hepatocellular Carcinoma
Peiqiang Jiang1, Wei Han1, Yu Fu1
1Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
Insights
Circular RNA hsa_circ_0091579 (circ_0091579) promotes hepatocellular carcinoma (HCC) development by regulating the miR-940/TACR1 axis. Knockdown of circ_0091579 inhibits HCC progression and tumor growth, revealing a novel mechanism in HCC pathogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
- The specific circRNA hsa_circ_0091579 (circ_0091579) is dysregulated in hepatocellular carcinoma (HCC).
- The precise mechanism by which circ_0091579 influences HCC progression remains largely unelucidated.
Purpose of the Study:
- To investigate the role and underlying mechanism of circ_0091579 in the development of hepatocellular carcinoma (HCC).
- To explore the regulatory relationship between circ_0091579, microRNA-940 (miR-940), and tachykinin-1 receptor (TACR1) in HCC.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction and Western blot were used to measure gene and protein expression.
- Cellular assays (viability, migration, invasion, colony formation, cell cycle, apoptosis) were performed to assess functional impacts.
- Dual-luciferase reporter assays confirmed interactions between circ_0091579, miR-940, and TACR1.
- In vivo xenograft models were utilized to evaluate the anti-tumor effects of circ_0091579 knockdown.
Main Results:
- circ_0091579 expression was significantly elevated in HCC tissues and cells.
- Silencing circ_0091579 suppressed HCC cell proliferation, migration, invasion, and colony formation, while inducing apoptosis and cell cycle arrest.
- circ_0091579 directly targets miR-940, and miR-940 targets TACR1, forming a regulatory axis that influences HCC development.
- Knockdown of circ_0091579 inhibited tumor growth in vivo.
Conclusions:
- circ_0091579 promotes HCC progression by regulating the miR-940/TACR1 axis.
- Downregulation of circ_0091579 exhibits anti-tumor effects in HCC.
- These findings highlight a novel pathogenic mechanism of circ_0091579 in hepatocellular carcinoma.
Purpose:
Circular RNAs (circRNAs) play important roles in hepatocellular carcinoma (HCC) development. The circRNA hsa_circ_0091579 (circ_0091579) is dysregulated in HCC, while the mechanism of circ_0091579 in HCC development is largely unknown.
Patients And Methods:
Thirty paired cancer and adjacent normal tissues were harvested from HCC patients. SNU-387 and Huh7 cells were cultured in this study. circ_0091579, microRNA-940 (miR-940) and tachykinin-1 receptor (TACR1) abundances were measured via quantitative reverse transcription-polymerase chain reaction or Western blot. Cell viability, migration, invasion, colony ability, cell cycle distribution and apoptosis were assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell assay, colony formation assay and flow cytometry. The interaction among circ_0091579, miR-940 and TACR1 was tested via dual-luciferase reporter analysis. The anti-HCC role of circ_0091579 knockdown in vivo was investigated using xenograft model.
Results:
circ_0091579 expression was enhanced in HCC tissue samples and cells. circ_0091579 silence inhibited cell viability, migration, invasion and colony formation, induced cell cycle arrest at G0/G1 phase, and promoted apoptosis in HCC cells. miR-940 was targeted via circ_0091579 and miR-940 knockdown reversed the suppressive effect of circ_0091579 silence on HCC development. miR-940 targeted TACR1 to repress HCC development. circ_0091579 could regulate TACR1 expression by mediating miR-940. Down-regulation of circ_0091579 decreased xenograft tumor growth.
Conclusion:
Knockdown of circ_0091579 repressed HCC development by mediating miR-940/TACR1 axis, indicating a new pathogenesis of HCC.
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