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XPD Regulates MIAT/miR-29a-3p/COL4A1 Axis to Impede Hepatocellular Carcinoma Development
Qi Wang1, Qichao Ruan2, Hao Ding1
1Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Abstract:
Xeroderma pigmentosum group D (XPD) has been reported to inhibit cell growth of hepatocellular carcinoma (HCC). This work attempted to reveal the underlying mechanism of XPD in HCC. In this study, XPD and miR-29a-3p were down-regulated, and MIAT and COL4A1 were up-regulated in tumor tissues of HCC patients. The same phenomena were also observed in HCC cell lines. XPD overexpression enhanced E-cadherin expression, reduced N-cadherin and Vimentin expression, and repressed the migration and invasion of HepG2 and Hep3B cells. MIAT or COL4A1 overexpression reversed the effect of XPD on the invasion, migration, and epithelial-mesenchymal transition (EMT) of HCC cells. MIAT overexpression-mediated promotion of malignant phenotypes of HCC cells was reversed by COL4A1 deficiency. In terms of mechanics, MIAT enhanced COL4A1 expression by sponging miR-29a-3p. XPD interacted with P53. XPD overexpression repressed MIAT expression, which was abrogated by P53 silencing. Thus, XPD recruited P53 to repress MIAT expression. In vivo, XPD up-regulation inhibited tumor growth and reduced the metastatic lesions in intrahepatic, lung, and kidney tissues of mice. In conclusion, this study demonstrated that XPD recruited P53 to regulate the MIAT/miR-29a-3p/COL4A1 axis, which contributed to inhibiting migration, invasion, EMT, and metastasis of HCC. Thus, XPD may be a valuable target for HCC treatment.
Insights
Xeroderma pigmentosum group D (XPD) inhibits hepatocellular carcinoma (HCC) growth by regulating the MIAT/miR-29a-3p/COL4A1 pathway. XPD
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Xeroderma pigmentosum group D (XPD) is implicated in inhibiting hepatocellular carcinoma (HCC) cell growth.
- Understanding the molecular mechanisms of XPD in HCC is crucial for developing targeted therapies.
Purpose of the Study:
- To elucidate the underlying mechanism of XPD in regulating hepatocellular carcinoma (HCC) progression.
- To investigate the role of the XPD/P53/MIAT/miR-29a-3p/COL4A1 axis in HCC metastasis and epithelial-mesenchymal transition (EMT).
Main Methods:
- Analysis of XPD, miR-29a-3p, MIAT, and COL4A1 expression in HCC tissues and cell lines.
- Overexpression and silencing experiments to assess the functional impact of XPD, MIAT, and COL4A1 on HCC cell behavior.
- Investigation of molecular interactions between XPD, P53, MIAT, and miR-29a-3p using co-immunoprecipitation and luciferase assays.
- In vivo studies using mouse models to evaluate the effect of XPD on tumor growth and metastasis.
Main Results:
- XPD and miR-29a-3p were downregulated, while MIAT and COL4A1 were upregulated in HCC.
- XPD overexpression suppressed HCC cell migration, invasion, and EMT, while MIAT or COL4A1 overexpression reversed these effects.
- MIAT promoted COL4A1 expression by sponging miR-29a-3p.
- XPD recruited P53 to repress MIAT expression, inhibiting HCC progression.
- In vivo, XPD upregulation reduced tumor growth and metastasis in mice.
Conclusions:
- XPD, through P53 recruitment, regulates the MIAT/miR-29a-3p/COL4A1 axis to inhibit HCC migration, invasion, EMT, and metastasis.
- XPD demonstrates potential as a therapeutic target for hepatocellular carcinoma (HCC) treatment.
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