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miR-4484 suppresses hepatocellular carcinoma progression via targeting KIF2C
Jianyang Lin1,2, Yun Cai3, Zhihong Chen1
1Department of General Surgery, Zhenjiang First People's Hospital, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Abstract:
Aberrantly expressed microRNA-4484 (miR-4484) has recently garnered attention for its involvement in human diseases, but its specific role in hepatocellular carcinoma (HCC) remains largely unexplored. This study investigates the function of miR-4484 in HCC progression and its regulatory interaction with KIF2C. Analysis of the data from the TCGA-LIHC database revealed that miR-4484 expression is significantly downregulated in HCC tissues, with lower levels correlating with worse prognosis. In vitro experiments confirmed that miR-4484 expression is lower in HCC cell lines compared to a normal liver cell line. Functional assays demonstrated that miR-4484 overexpression via a miR-4484 mimic suppressed cell proliferation and induced G1 phase arrest, whereas miR-4484 inhibition promoted proliferation and facilitated cell cycle progression from G1 to S and G2 phases. Additionally, KIF2C expression was significantly upregulated in HCC tissues and cell lines, exhibiting an inverse correlation with miR-4484 levels. Dual-Luciferase Reporter Assays confirmed that miR-4484 directly binds to KIF2C, thereby regulating its expression and influencing cell proliferation and cell cycle progression. In vivo, subcutaneous intratumoral injection of the miR-4484 mimic in nude mice significantly inhibited HCC tumour growth. These findings highlight miR-4484 as a potential tumour suppressor in HCC through its direct targeting of KIF2C, underscoring its promise as a therapeutic target for HCC treatment.
Insights
MicroRNA-4484 (miR-4484) acts as a tumor suppressor in hepatocellular carcinoma (HCC) by inhibiting cell proliferation and tumor growth. It targets KIF2C, offering a potential therapeutic strategy for HCC treatment.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Aberrant microRNA-4484 (miR-4484) expression is implicated in diseases, but its role in hepatocellular carcinoma (HCC) is understudied.
- Hepatocellular carcinoma (HCC) is a significant global health concern with a need for novel therapeutic targets.
Purpose of the Study:
- To investigate the function of miR-4484 in HCC progression.
- To elucidate the regulatory relationship between miR-4484 and KIF2C in HCC.
- To evaluate miR-4484 as a potential therapeutic agent for HCC.
Main Methods:
- Bioinformatic analysis of TCGA-LIHC database for miR-4484 and KIF2C expression.
- In vitro studies using HCC cell lines to assess miR-4484 effects on proliferation and cell cycle.
- Dual-Luciferase Reporter Assays to confirm direct binding of miR-4484 to KIF2C.
- In vivo experiments in nude mice using miR-4484 mimics to evaluate tumor growth inhibition.
Main Results:
- miR-4484 was significantly downregulated in HCC tissues and cell lines, correlating with poor prognosis.
- miR-4484 overexpression suppressed HCC cell proliferation and induced G1 phase arrest.
- KIF2C was upregulated in HCC and inversely correlated with miR-4484 levels.
- miR-4484 directly targeted KIF2C, inhibiting its expression and downstream effects.
- In vivo administration of miR-4484 mimic significantly reduced HCC tumor growth in mice.
Conclusions:
- miR-4484 functions as a tumor suppressor in HCC by targeting KIF2C.
- Restoring miR-4484 levels inhibits HCC progression and tumor growth.
- miR-4484 represents a promising therapeutic target for hepatocellular carcinoma treatment.
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