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CircHIPK3 modulates VEGF through MiR-7 to affect ovarian cancer cell proliferation and apoptosis
Heling Zhou1, Jie Li, Xiaoli Lai
1Department of Gynecology, Taizhou Hospital, #150 Ximen Ave, Linhai, Zhejiang 317000, China.
Purpose:
The purpose of this study was to observe the effects of circHIPK3on the proliferation and apoptosis of ovarian cancer cells, and to further explore the potential mechanism therein.
Methods:
CircHIPK3 was determined in the carcinoma tissues, normal adjacent tissues, and also in ovarian cancer cells via RT-PCR. The proliferation and apoptosis of cells were observed via colony-forming assay, 5-ethynyl-2'-deoxyuridine (EdU) staining and Western blotting. Moreover, the effect of the inhibition of circHIPK3 on the in vivo growth of ovarian cancer cells was detected using subcutaneous tumorigenesis assay. Finally, the effect of circHIPK3 on the expression of the micro ribonucleic acid (miR)-7/vascular endothelial growth factor (VEGF) signaling pathway in ovarian cancer cells was examined.
Results:
CircHIPK3 in the carcinoma tissues was obviously higher than that in normal adjacent tissues. SKOV3 cell lines transfected with circHIPK3 inhibitor exhibited declined number of colonies. The inhibition of circHIPK3 distinctly suppressed the expression of B-cell lymphoma 2 (Bcl-2) and raised that of Bcl-2 associated X protein (Bax). Besides, the inhibition of circHIPK3 obviously weakened the tumorigenicity of ovarian cancer cells subcutaneously transplanted. Finally, it was found that miR-7 declined obviously and VEGF rose distinctly in the carcinoma tissues, and the in vitro assay verified the obvious increase in the expression of miR-7 and the prominently inhibited VEGF protein expression in the ovarian cancer cells with the inhibition of circHIPK3.
Conclusions:
CircHIPK3 has an obviously increased expression level in the carcinoma tissues of ovarian cancer patients, and the inhibition of circHIPK3 can activate the miR-7-mediated decline in the expression of VEGF to repress the proliferation and promote the apoptosis of ovarian cancer cells.
Insights
Circular HIPK3 (circHIPK3) is upregulated in ovarian cancer. Inhibiting circHIPK3 suppresses tumor growth and promotes apoptosis by activating the miR-7/VEGF pathway.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Ovarian cancer is a leading cause of cancer-related deaths in women.
- Circular RNAs (circRNAs) are emerging as critical regulators in various cancers, including ovarian cancer.
- The specific role of circHIPK3 in ovarian cancer progression remains largely unexplored.
Purpose of the Study:
- To investigate the functional role of circHIPK3 in ovarian cancer cell proliferation and apoptosis.
- To elucidate the underlying molecular mechanism involving the miR-7/VEGF signaling pathway.
Main Methods:
- Quantitative RT-PCR to determine circHIPK3 expression in tissues and cells.
- Colony-forming, EdU staining, and Western blotting assays to assess cell proliferation and apoptosis.
- Subcutaneous tumorigenesis assay to evaluate in vivo tumor growth.
- In vitro assays to examine the miR-7/VEGF signaling pathway.
Main Results:
- CircHIPK3 expression was significantly higher in ovarian carcinoma tissues than in normal tissues.
- Inhibition of circHIPK3 reduced colony formation, suppressed Bcl-2, and increased Bax expression.
- Reduced circHIPK3 expression weakened tumor growth in vivo.
- CircHIPK3 inhibition led to decreased miR-7 and increased VEGF expression in tumor tissues, while in vitro assays showed increased miR-7 and decreased VEGF.
Conclusions:
- CircHIPK3 is overexpressed in ovarian cancer tissues.
- Inhibiting circHIPK3 represses ovarian cancer cell proliferation and promotes apoptosis.
- CircHIPK3 regulates ovarian cancer progression via the miR-7/VEGF pathway.
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