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Published on: April 25, 2018
MicroRNA-493 suppresses hepatocellular carcinoma tumorigenesis through down-regulation of anthrax toxin receptor 1
Yuqiang Xu1, Kuikui Ge2, Junhao Lu1
1State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
Abstract:
Hepatocellular carcinoma (HCC) is known as a highly prevalent cancer with a poor prognosis and short survival time, despite intensive research and clinical efforts. Increasing numbers of studies have reported that microRNAs are involved in the malignant behavior of hepatocellular carcinoma cells via directly targeting multiple oncogenes or tumor suppressors. Here, we report that the expression of microRNA-493 (miR-493) is decreased in HCC cell lines and in tumor tissues. Overexpression of miR-493 in HCC cells dramatically inhibited cell proliferation and colony-formation in vitro and inhibited tumor formation of HCC cell xenografts in vivo. miR-493 also suppressed cell migration and invasion in HCC cell lines. Novel targets ANTXR1 and RSPO2 were confirmed to be suppressed by miR-493 directly, and overexpression of ANTXR1 and RSPO2 could restore tumorigenesis in miR-493 treated HCC cell. Moreover, Wnt/β-catenin signaling pathway, which was reported to be activated by ANTXR1 and RSPO2, was also inhibited by miR-493 overexpression and might be involved in anti-tumor function of miR-493. These findings suggest that miR-493 acts as a negative regulator in hepatocellular carcinoma progression and may be a potential therapeutic target for HCC.
Insights
MicroRNA-493 (miR-493) is downregulated in hepatocellular carcinoma (HCC). Restoring miR-493 inhibits HCC cell growth, migration, and invasion, suggesting its potential as a therapeutic target for liver cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) is a prevalent cancer with poor outcomes.
- MicroRNAs play roles in cancer by targeting oncogenes and tumor suppressors.
- The specific role of microRNA-493 (miR-493) in HCC remains to be fully elucidated.
Purpose of the Study:
- To investigate the expression and function of miR-493 in hepatocellular carcinoma.
- To identify the targets and signaling pathways regulated by miR-493 in HCC.
- To evaluate the therapeutic potential of miR-493 in HCC.
Main Methods:
- Quantitative real-time PCR to assess miR-493 expression in HCC cell lines and tissues.
- In vitro assays (proliferation, colony formation, migration, invasion) to evaluate miR-493 function.
- In vivo xenograft models to assess tumor formation.
- Western blotting and luciferase reporter assays to confirm direct targets (ANTXR1, RSPO2) and pathway inhibition (Wnt/β-catenin).
Main Results:
- miR-493 expression was significantly decreased in HCC cell lines and tumor tissues.
- Overexpression of miR-493 inhibited HCC cell proliferation, colony formation, migration, and invasion in vitro.
- miR-493 overexpression suppressed HCC tumor growth in vivo.
- ANTXR1 and RSPO2 were identified as direct targets of miR-493, and their overexpression rescued HCC phenotypes.
- miR-493 inhibited the Wnt/β-catenin signaling pathway.
Conclusions:
- miR-493 functions as a tumor suppressor in hepatocellular carcinoma.
- miR-493 inhibits HCC progression by targeting ANTXR1 and RSPO2, subsequently suppressing the Wnt/β-catenin pathway.
- miR-493 represents a potential therapeutic target for HCC treatment.
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