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Updated: May 8, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-503 inhibits the G1/S transition by downregulating cyclin D3 and E2F3 in hepatocellular carcinoma
Fenqiang Xiao1, Wu Zhang, Liming Chen
1Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, P.R. China.
Background:
Increasing evidence indicates that deregulation of microRNAs (miRNAs) is involved in tumorigenesis. Downregulation of microRNA-503 has been observed in various types of diseases, including cancer. However, the biological function of miR-503 in hepatocellular carcinoma (HCC) is still largely unknown. In this study we aimed to elucidate the prognostic implications of miR-503 in HCC and its pathophysiologic role.
Methods:
Quantitative reverse transcriptase polymerase chain reaction was used to evaluate miR-503 expression in HCC tissues and cell lines. Western blotting was performed to evaluate the expression of the miR-503 target genes. In vivo and in vitro assays were performed to evaluate the function of miR-503 in HCC. Luciferase reporter assay was employed to validate the miR-503 target genes.
Results:
miR-503 was frequently downregulated in HCC cell lines and tissues. Low expression levels of miR-503 were associated with enhanced malignant potential such as portal vein tumor thrombi, histologic grade, TNM stage, AFP level and poor prognosis. Multivariate analysis indicated that miR-503 downregulation was significantly associated with worse overall survival of HCC patients. Functional studies showed miR-503 suppressed the proliferation of HCC cells by induction of G1 phase arrest through Rb-E2F signaling pathways, and thus may function as a tumor suppressor. Further investigation characterized two cell cycle-related molecules, cyclin D3 and E2F3, as the direct miR-503 targets.
Conclusion:
Our data highlight an important role for miR-503 in cell cycle regulation and in the molecular etiology of HCC, and implicate the potential application of miR-503 in prognosis prediction and miRNA-based HCC therapy.
Insights
MicroRNA-503 (miR-503) is frequently downregulated in hepatocellular carcinoma (HCC), acting as a tumor suppressor by inhibiting cell proliferation. Low miR-503 levels indicate poor prognosis in HCC patients, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) play a role in tumorigenesis, with miR-503 downregulation observed in various cancers.
- The specific function of miR-503 in hepatocellular carcinoma (HCC) remains largely unexplored.
Purpose of the Study:
- To investigate the prognostic significance of miR-503 in HCC.
- To elucidate the pathophysiological role of miR-503 in HCC development and progression.
Main Methods:
- Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess miR-503 expression in HCC tissues and cell lines.
- Western blotting and luciferase reporter assays to identify and validate miR-503 target genes.
- In vivo and in vitro functional assays to determine the role of miR-503 in HCC cell behavior.
Main Results:
- miR-503 expression was significantly downregulated in HCC tissues and cell lines.
- Low miR-503 levels correlated with advanced tumor features (e.g., portal vein tumor thrombi, high TNM stage, elevated AFP) and poorer patient survival.
- Functional studies revealed miR-503 suppresses HCC cell proliferation by inducing G1 phase arrest via the Rb-E2F pathway, identifying cyclin D3 and E2F3 as direct targets.
Conclusions:
- miR-503 functions as a tumor suppressor in HCC by regulating cell cycle progression.
- Downregulation of miR-503 is a prognostic marker for HCC.
- miR-503 holds potential for use in HCC prognosis prediction and miRNA-based therapeutic strategies.
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