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The circular RNA circ-ITCH suppresses ovarian carcinoma progression through targeting miR-145/RASA1 signaling
Jinghui Hu1, Li Wang2, Jiming Chen3
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China; Department of Gynecology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Abstract:
As the leading cause of death for gynecological cancers, ovarian cancer (OC) ranks fifth overall for cancer-related death among women. Emerging evidence has indicated that circular RNA (circRNA), recognized as functional non-coding transcripts in eukaryotic cells, may be involved in many physiological or pathological processes. It was reported that circ-ITCH is downregulated in multi cancers and serves as a powerful tumor suppressor among through a competing endogenous RNA (ceRNA) pathway. However, the existence and the role of circ-ITCH in OC was not reported. Here, we found a broad down-regulation of circ-ITCH in OC tissues and cells, which correlates with a worse prognosis in OC patients. Functional studies suggest that circ-ITCH overexpression inhibits the cell viability and motility by CCK8, cell cycle, wound healing assay and invasion assay. It also inhibits the tumorigenesis ability in xenograft NOD mice in vivo. Mechanically, we demonstrated that circ-TCH acts as a ceRNA to sponge miR-145, increases the level of RASA1, and inhibits the malignant progression of OC cells via the circ-ITCH-miR-145-RASA1 axis in vitro and in vivo. Taken together, our findings provide a novel tumor suppressive role regarding circ-ITCH function in the malignant progression of OC.
Insights
Circular RNA (circRNA) circ-ITCH is downregulated in ovarian cancer (OC), suppressing tumor growth and progression. This study reveals circ-ITCH as a novel tumor suppressor in OC via the circ-ITCH-miR-145-RASA1 axis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian cancer (OC) is a leading cause of gynecological cancer death.
- Circular RNAs (circRNAs) are emerging as key regulators in various cellular processes.
- circ-ITCH, a known tumor suppressor in other cancers, has not been studied in OC.
Purpose of the Study:
- To investigate the role of circ-ITCH in ovarian cancer.
- To elucidate the underlying molecular mechanisms of circ-ITCH in OC progression.
Main Methods:
- Analysis of circ-ITCH expression in OC tissues and cells.
- Functional assays including CCK8, cell cycle, wound healing, and invasion assays.
- In vivo tumorigenesis studies in xenograft NOD mice.
- Mechanistic studies involving RNA immunoprecipitation and luciferase reporter assays to confirm the circ-ITCH-miR-145-RASA1 axis.
Main Results:
- circ-ITCH was broadly downregulated in OC tissues and cells, correlating with poor patient prognosis.
- Overexpression of circ-ITCH inhibited OC cell viability, motility, and tumorigenesis in vitro and in vivo.
- circ-ITCH functions as a competing endogenous RNA (ceRNA) by sponging miR-145, thereby increasing RASA1 levels.
- The circ-ITCH-miR-145-RASA1 axis was confirmed to inhibit OC cell malignant progression.
Conclusions:
- circ-ITCH exhibits a novel tumor-suppressive role in ovarian cancer.
- The circ-ITCH-miR-145-RASA1 axis represents a potential therapeutic target for OC treatment.
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