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Circular RNA hsa_circ_0007444 inhibits ovarian cancer progression through miR-23a-3p/DICER1 axis
Min Zhang1,2, Yu Sun1, Hanzi Xu3
1Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, China.
Abstract:
Ovarian cancer is the second leading cause of death in women with gynecological malignancy in China. Circular RNAs are a class of noncoding regulatory RNAs reported to be involved in cancer development and progression. Previous studies, including our own, have indicated that hsa_circ_0007444 is downregulated in ovarian cancer tissues. This study aims to elucidate the function and mechanism of hsa_circ_0007444 in ovarian cancer progression. The expression of hsa_circ_0007444 is determined by quantitative real-time PCR (qRT-PCR). Cell proliferation, invasion, migration and apoptosis are examined by cell counting-kit 8 (CCK-8), transwell and flow cytometry assays. Tumor growth and metastasis are assessed in vivo using Balb/c nude mouse xenograft model and tail vein injection model. And the mechanism of action of hsa_circ_0007444 is analysed by RNA-binding protein immunoprecipitation (RIP), luciferase reporter and rescue assays. hsa_circ_0007444 is downregulated in ovarian cancer tissues and cell lines compared with that in normal ovarian tissues and normal epithelial cell line. Gain- and loss-of-function results indicate that hsa_circ_0007444 inhibits cell proliferation, invasion, migration and increases cell apoptosis of ovarian cancer cells in vitro, and inhibits tumor growth and lung metastasis in vivo. Mechanistically, hsa_circ_0007444 can interact with AGO2 and sponge miR-23a-3p, thereby upregulating DICER1 expression, which is an important tumor suppressor in ovarian cancer. And miR-23a-3p mimics can rescue the inhibitory effect of hsa_circ_0007444 on ovarian cancer cell proliferation, invasion and migration. Therefore, hsa_circ_0007444 can inhibit ovarian cancer progression through the hsa_circ_0007444/miR-23a-3p/DICER1 axis.
Insights
Circular RNAs like hsa_circ_0007444 are downregulated in ovarian cancer. This study shows hsa_circ_0007444 inhibits ovarian cancer progression by regulating the miR-23a-3p/DICER1 axis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian cancer remains a leading cause of gynecological cancer mortality in China.
- Circular RNAs (circRNAs) are implicated in cancer development, with some found to be downregulated in ovarian cancer.
- hsa_circ_0007444 has been previously identified as downregulated in ovarian cancer tissues.
Purpose of the Study:
- To investigate the functional role of hsa_circ_0007444 in ovarian cancer progression.
- To elucidate the underlying molecular mechanism of hsa_circ_0007444 in ovarian cancer.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for expression analysis.
- In vitro assays (CCK-8, Transwell, flow cytometry) for cell proliferation, invasion, migration, and apoptosis.
- In vivo mouse models (xenograft, tail vein injection) for tumor growth and metastasis assessment.
- Molecular mechanism analysis using RNA-binding protein immunoprecipitation (RIP), luciferase reporter, and rescue assays.
Main Results:
- hsa_circ_0007444 expression was significantly downregulated in ovarian cancer tissues and cell lines.
- Overexpression of hsa_circ_0007444 suppressed ovarian cancer cell proliferation, invasion, and migration, while promoting apoptosis in vitro.
- hsa_circ_0007444 inhibited tumor growth and lung metastasis in vivo.
- Mechanistically, hsa_circ_0007444 interacts with AGO2, sponges miR-23a-3p, and upregulates DICER1, a tumor suppressor.
Conclusions:
- hsa_circ_0007444 functions as a tumor suppressor in ovarian cancer.
- The hsa_circ_0007444/miR-23a-3p/DICER1 axis plays a crucial role in inhibiting ovarian cancer progression.
- hsa_circ_0007444 holds potential as a therapeutic target for ovarian cancer treatment.
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