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Updated: Jan 26, 2026
Author Spotlight: Investigating Liver Cancer Pathogenesis Using Patient-Derived Organoids
Published on: August 18, 2023
miR-1-3p suppresses proliferation of hepatocellular carcinoma through targeting SOX9
Hao Zhang1, Zhenya Zhang2, Lili Gao3
1Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, People's Republic of China, yubo120@126.com, mryangtao@sina.com.
Background:
Liver cancer was the fourth leading cause of cancer-related death in 2015. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. miR-1-3p plays important roles in cancer, including prostate, bladder, lung cancer, and colorectal carcinoma. The function of miR-1-3p in HCC remains poorly understood.
Methods:
qRT-PCR was performed to detect the miR-1-3p expression in HCC cell lines (HCCLM3, Hep3B, Bel-7404, SMMC-7721) and the normal human hepatic cell line (LO2). HCCLM3 and Bel-7404 cells were transfected with miR-1-3p mimic or scramble control followed by water-soluble tetrazolium salt (WST-1) assay. Western bolt analysis was performed to determine the protein levels. TargetScan7.1 (http://www.targetscan.org/vert_71/) was used to predict the potential targets of miR-1-3p. SRY (sex determining region Y)-box 9 (SOX9), which has been previously shown to play an important role in HCC, was found to be a target of miR-1-3p. Luciferase reporter assay was used to explore the targeting of miR-1-3p on SOX9. For in vivo tumorigenesis assay, HCCLM3 cells with stable overexpression of miR-1-3p or control plasmid were injected subcutaneously into the flank of the SCID mice and animals were monitored for tumor growth.
Results:
miR-1-3p was significantly downregulated in HCC cell lines (HCCLM3, Hep3B, Bel-7404, and SMMC-7721) compared to normal human hepatic cell line (LO2). Overexpression of miR-1-3p significantly inhibited the proliferation and induced apoptosis in HCCLM3 and Bel-7474 cells. SOX9 was a direct target of miR-1-3p in HCC cells. Inhibition of SOX9 significantly inhibited the proliferation of HCCLM3 and Bel-7474 cells. In vivo, overexpression of miR-1-3p decreased tumor volume in a xenograft model.
Conclusion:
These results highlight the role of miR-1-3p in HCC. Overexpression of miR-1-3P inhibited the proliferation of HCC at least partly due to the regulation of SOX9. miR-1-3p may be a promising therapeutic candidate for HCC.
Insights
MicroRNA-1-3p (miR-1-3p) is downregulated in hepatocellular carcinoma (HCC). Its overexpression inhibits HCC cell proliferation and tumor growth by targeting SOX9, suggesting miR-1-3p as a potential therapeutic for liver cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer death.
- The role of microRNA-1-3p (miR-1-3p) in HCC pathogenesis is not well understood.
- miR-1-3p is implicated in various cancers, but its specific function in liver cancer requires elucidation.
Purpose of the Study:
- To investigate the expression and function of miR-1-3p in hepatocellular carcinoma (HCC).
- To identify potential targets of miR-1-3p in HCC.
- To evaluate the therapeutic potential of miR-1-3p in HCC models.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess miR-1-3p expression in HCC cell lines.
- Cell proliferation assays (WST-1) and apoptosis analysis following miR-1-3p mimic transfection.
- Western blot and luciferase reporter assays to validate SOX9 as a direct miR-1-3p target.
- In vivo xenograft models to assess the effect of miR-1-3p on tumor growth.
Main Results:
- miR-1-3p expression was significantly downregulated in HCC cell lines compared to normal liver cells.
- Overexpression of miR-1-3p suppressed HCC cell proliferation and induced apoptosis.
- SRY (sex determining region Y)-box 9 (SOX9) was confirmed as a direct target of miR-1-3p.
- Inhibition of SOX9 mimicked the anti-proliferative effects of miR-1-3p.
- In vivo studies showed that miR-1-3p overexpression reduced tumor volume.
Conclusions:
- miR-1-3p acts as a tumor suppressor in HCC.
- The tumor-suppressive function of miR-1-3p is partly mediated through the regulation of SOX9.
- miR-1-3p represents a promising therapeutic candidate for hepatocellular carcinoma.
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