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Published on: June 17, 2014
CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/β-catenin pathway
Minnan Wang1, Bo Chen2, Zixuan Ru1
1Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, Heilongjiang Province, China.
Abstract:
While recent evidence has uncovered that circular RNAs (circRNAs) are vital regulators of carcinogenesis, their role in papillary thyroid cancer (PTC) is not clearly understood. In this study, we reveal that lower levels of circRNA circ-ITCH are expressed in PTC tissues than in normal adjacent tissues. Gain-of-functional assays show that circ-ITCH overexpression suppresses PTC cell proliferation and invasion and promotes apoptosis in vitro. Overexpression of circ-ITCH also leads to impaired tumor growth in vivo. Bioinformatics analysis and luciferase reporter assays demonstrate that circ-ITCH sponges miR-22-3p to upregulate the expression of CBL, an E3 ligase of nuclear β-catenin. Elevated levels of CBL suppress activation of the Wnt/β-catenin pathway and consequently attenuates PTC progression. In summary, our study reveals a novel signaling pathway of circ-ITCH/miR-22-3p/CBL/β-catenin involved in PTC development and progression.
Insights
This study reveals that low levels of circular RNA circ-ITCH in papillary thyroid cancer (PTC) promote tumor growth. Restoring circ-ITCH suppresses cancer progression by inhibiting the circ-ITCH/miR-22-3p/CBL/β-catenin pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are emerging regulators in carcinogenesis.
- The specific role of circRNAs in papillary thyroid cancer (PTC) remains largely undefined.
Purpose of the Study:
- To investigate the function of circRNA circ-ITCH in PTC development.
- To elucidate the underlying molecular mechanisms of circ-ITCH in PTC.
Main Methods:
- Quantitative real-time PCR to measure circ-ITCH expression.
- In vitro gain-of-functional assays (cell proliferation, invasion, apoptosis).
- In vivo tumor growth assays.
- Bioinformatics analysis and luciferase reporter assays to identify miRNA targets and downstream pathways.
Main Results:
- Circ-ITCH expression is significantly downregulated in PTC tissues compared to normal adjacent tissues.
- Overexpression of circ-ITCH inhibits PTC cell proliferation and invasion, and promotes apoptosis in vitro.
- Circ-ITCH overexpression impairs tumor growth in vivo.
- Circ-ITCH acts as a sponge for miR-22-3p, upregulating CBL expression.
- CBL upregulation suppresses the Wnt/β-catenin pathway, attenuating PTC progression.
Conclusions:
- Circ-ITCH functions as a tumor suppressor in PTC.
- A novel circ-ITCH/miR-22-3p/CBL/β-catenin signaling pathway is identified in PTC progression.
- Circ-ITCH represents a potential therapeutic target for PTC.
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