WT1-AS promotes cell apoptosis in hepatocellular carcinoma through down-regulating of WT1
Long Lv1, Gong Chen2, Jianping Zhou3
1Department of General Surgery, People's Hospital of Gaochun, No. 9 Chunzhong Road, Gaochun, Nanjing, 211300, Jiangsu Province, China. l3851596501@163.com.
Background:
The antisense of the tumor suppressor gene WT1 (WT1-AS) is a long non-coding RNA. The role of WT1-AS in the development of hepatocellular carcinoma (HCC) has not yet been elucidated.
Methods:
Quantitative real-time PCR and western blot analyses were used to measure levels of WT1-AS and its related genes in tumor and corresponding adjacent tumor tissues of HCC patients. The effect on HCC cell proliferation and apoptosis was assessed by EdU incorporation assays and PI-Annexin-V staining, respectively. ShRNA and dual-luciferase assays were used to investigate the regulatory relationship between WT1-AS and WT1 in cell lines.
Results:
WT1-AS expression correlated negatively with WT1 expression in HCC tumor tissue. Kaplan-Meier curve analysis revealed that WT1-AS expression is a reliable indicator of HCC prognosis. The downregulation of WT1 expression by WT1-AS promoted cell apoptosis by suppressing the JAK/STAT3 signaling pathway. Bioinformatics analysis showed that WT1-AS downregulates WT1 by binding to the TATA region of the WT1 promotor. WT1-AS was also able to reverse WT1-mediated resistance to Dox based chemotherapy in HCC cells.
Conclusions:
WT1-AS downregulates WT1 expression in HCC tumors and promotes apoptosis by binding to the promoter region of WT1. Our findings suggest that WT1-AS may function as a tumor suppressor in HCC by reversing the oncogenic effects of WT1.
Insights
The long non-coding RNA WT1-antisense (WT1-AS) acts as a tumor suppressor in hepatocellular carcinoma (HCC). WT1-AS downregulates WT1 expression, promoting apoptosis and improving prognosis in HCC patients.
Area of Science:
- Molecular biology
- Oncology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) is a significant global health concern.
- The role of the WT1-antisense (WT1-AS) long non-coding RNA in HCC development is largely unknown.
- WT1 is implicated in various cancers, but its specific role in HCC requires further investigation.
Purpose of the Study:
- To elucidate the function of WT1-AS in hepatocellular carcinoma (HCC).
- To investigate the regulatory relationship between WT1-AS and the WT1 gene in HCC.
- To determine the prognostic value of WT1-AS in HCC patients.
Main Methods:
- Quantitative real-time PCR and western blot to assess WT1-AS and WT1 expression levels.
- EdU incorporation and PI-Annexin-V staining to evaluate cell proliferation and apoptosis.
- ShRNA and dual-luciferase assays to explore the WT1-AS/WT1 regulatory axis.
- Bioinformatics and Kaplan-Meier analyses for prognostic assessment.
Main Results:
- WT1-AS expression was inversely correlated with WT1 expression in HCC tissues.
- Downregulation of WT1 by WT1-AS suppressed the JAK/STAT3 pathway, promoting apoptosis.
- WT1-AS binds to the WT1 promoter region, downregulating WT1 expression.
- WT1-AS expression serves as a favorable prognostic indicator for HCC patients.
- WT1-AS reversed Doxorubicin resistance in HCC cells.
Conclusions:
- WT1-AS functions as a tumor suppressor in HCC by downregulating WT1 expression.
- WT1-AS promotes apoptosis and may reverse oncogenic effects of WT1 in HCC.
- WT1-AS represents a potential therapeutic target for improving HCC prognosis.
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