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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-212 inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting FOXA1
Huahua Tu1, Gang Wei2, Qinghe Cai1
1Department of Hepatobiliary Surgery, Hubei University of Medicine, Shiyan, People's Republic of China.
Abstract:
MircroRNA-212 (miR-212) is proposed as a novel tumor-related miRNA and has been found to be significantly deregulated in human cancers. In this study, the miR-212 expression was found to be obviously downregulated in hepatocellular carcinoma (HCC) tissues as compared with adjacent nontumor tissues. Clinical association analysis indicated that low expression of miR-212 was prominently correlated with poor prognostic features of HCC, including high AFP level, large tumor size, high Edmondson-Steiner grading, and advanced tumor-node-metastasis tumor stage. Furthermore, the miR-212 expression was an independent prognostic marker for predicting both 5-year overall survival and disease-free survival of HCC patients. Our in vitro studies showed that upregulation of miR-212 inhibited cell proliferation and induced apoptosis in HepG2 cells. On the contrary, downregulation of miR-212 promoted cell proliferation and suppressed apoptosis in Huh7 cells. Interestingly, we found that upregulation of miR-212 decreased FOXA1 expression in HepG2 cells. Significantly, FOXA1 was identified as a direct target of miR-212 in HCC. FOXA1 was downregulated in HCC tissues as compared with noncancerous tissues. An inverse correlation between FOXA1 and miR-212 expression was observed in HCC tissues. Notably, FOXA1 knockdown inhibited cell proliferation and induced apoptosis in HepG2 cells. In conclusion, miR-212 is a potent prognostic marker and may suppress HCC tumor growth by inhibiting FOXA1 expression.
Insights
MicroRNA-212 (miR-212) is downregulated in hepatocellular carcinoma (HCC), correlating with poor prognosis. Upregulating miR-212 inhibits HCC cell growth by targeting FOXA1, suggesting miR-212 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression implicated in various cancers.
- MicroRNA-212 (miR-212) is a novel miRNA with potential roles in tumorigenesis.
- Dysregulation of miRNAs is frequently observed in hepatocellular carcinoma (HCC).
Purpose of the Study:
- To investigate the role of miR-212 in hepatocellular carcinoma (HCC).
- To determine the prognostic significance of miR-212 in HCC patients.
- To elucidate the molecular mechanism underlying miR-212's function in HCC.
Main Methods:
- Quantitative real-time PCR to assess miR-212 expression in HCC tissues and cell lines.
- Clinical data analysis to correlate miR-212 expression with patient prognosis.
- In vitro cell proliferation and apoptosis assays (e.g., HepG2, Huh7 cells).
- Western blot and luciferase reporter assays to validate direct targeting of FOXA1 by miR-212.
Main Results:
- miR-212 was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues.
- Low miR-212 expression correlated with poor prognostic factors (high AFP, large tumor size, advanced stage).
- miR-212 expression served as an independent prognostic marker for overall and disease-free survival in HCC.
- Overexpression of miR-212 inhibited proliferation and induced apoptosis in HCC cells, while downregulation promoted these effects.
- FOXA1 was identified as a direct target of miR-212, and its expression was inversely correlated with miR-212 in HCC.
- Knockdown of FOXA1 mimicked the tumor-suppressive effects of miR-212 upregulation.
Conclusions:
- miR-212 acts as a tumor suppressor in HCC.
- miR-212 is a potent independent prognostic biomarker for HCC.
- miR-212 may exert its tumor-suppressive function by inhibiting FOXA1 expression in HCC.
- Targeting miR-212 or its pathway presents a potential therapeutic strategy for HCC.
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