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CircITGA7 overexpression suppresses HCC progression via miR-330/BCL11B axis regulation
Zhijie Li1, Hui Ren1, Shuaishuai Tan2
1Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100039, China.
Abstract:
As a kind of prevalent malignancy globally, hepatocellular carcinoma (HCC) is characterized by significant morbidity and mortality due to the difficulties in early diagnosis and limited treatment options. Circular RNAs (circRNAs) are a type of circular single-stranded RNA molecule formed by the back-splicing of the 5' end and the 3' end of linear RNA, possessing multiple biological functions. In recent years, numerous reports have demonstrated that circRNAs are potential biomarkers and therapeutic targets for HCC. In this study, we found that circITGA7 is significantly downregulated in HCC tissue compared to adjacent non-tumor tissue. Functional experiments such as CCK8, EdU, colony formation and wound healing assays proved that overexpression of circITGA7 can effectively inhibit the proliferation, migration and invasion of HCC cells. Further research found that circITGA7 can inhibit miR-330 to release BCL11B expression, thereby promoting P53 expression, blocking the cell cycle and promoting apoptosis in HCC cells. In addition, circITGA7 can impede the proliferation of HCC cells in vivo. Therefore, circITGA7 is a potential biomarker for the diagnosis of HCC development and a potential target for the treatment of HCC.
Insights
Circular RNA ITGA7 (circITGA7) is downregulated in hepatocellular carcinoma (HCC). Overexpressing circITGA7 inhibits HCC cell growth, migration, and invasion, suggesting its potential as a diagnostic biomarker and therapeutic target for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) is a prevalent global malignancy with high mortality.
- Early diagnosis and effective treatments for HCC remain challenging.
- Circular RNAs (circRNAs) are emerging as critical regulators and potential biomarkers in various cancers, including HCC.
Purpose of the Study:
- To investigate the role of circRNA ITGA7 (circITGA7) in hepatocellular carcinoma (HCC).
- To explore circITGA7 as a potential diagnostic biomarker and therapeutic target for HCC.
Main Methods:
- Quantitative real-time PCR to assess circITGA7 expression levels in HCC tissues.
- In vitro functional assays (CCK8, EdU, colony formation, wound healing) to evaluate the effects of circITGA7 on HCC cell proliferation, migration, and invasion.
- Western blotting to analyze protein expression levels (miR-330, BCL11B, P53).
- In vivo tumor xenograft models to assess the impact of circITGA7 on HCC growth.
Main Results:
- circITGA7 was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues.
- Overexpression of circITGA7 suppressed HCC cell proliferation, migration, and invasion in vitro.
- circITGA7 was found to inhibit miR-330, leading to increased BCL11B and P53 expression, cell cycle arrest, and apoptosis.
- circITGA7 overexpression inhibited HCC cell proliferation in vivo.
Conclusions:
- circITGA7 functions as a tumor suppressor in HCC by regulating the miR-330/BCL11B/P53 axis.
- circITGA7 holds promise as a diagnostic biomarker and a potential therapeutic target for hepatocellular carcinoma.
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