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Circ-SKA3 upregulates ID3 expression by decoying miR-326 to accelerate the development of medulloblastoma
Xinde Zhao1, Jianwei Guan1, Minjie Luo1
1Department of Pediatric Neurosurgery, ZhuJiang Hospital of Southern Medical University, Guangzhou 510282, China.
Abstract:
Medulloblastoma (MB), the most common malignant childhood brain tumor, is a serious threat to life. Circular RNA (circRNA) is involved in the development of various cancers, including MB. We aimed to explore the role of circRNA spindle and kinetochore associated complex subunit 3 (circ-SKA3) in MB progression. Circ-SKA3 expression was elevated in MB tissues and cells. Depleted expression of circ-SKA3 inhibited MB cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest, and circ-SKA3 knockdown inhibited MB growth in vivo. Mechanism analyses revealed that circ-SKA3 directly targeted miR-326 that could bind to ID3, and circ-SKA3 decoyed miR-326 to increasing ID3 expression. Rescue experiments showed that miR-326 inhibition reversed the effects of circ-SKA3 knockdown, and ID3 overexpression recovered MB cell proliferation, migration and invasion blocked by miR-326 restoration. In conclusion, circ-SKA3 functioned as an oncogene to promote the development of MB by increasing ID3 expression via decoying miR-326, hinting that circ-SKA3 might be a therapeutic target of MB.
Insights
Circular RNA spindle and kinetochore associated complex subunit 3 (circ-SKA3) promotes childhood medulloblastoma (MB) growth by increasing ID3 expression. Inhibiting circ-SKA3 may offer a new therapeutic strategy for MB.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Medulloblastoma (MB) is the most common malignant childhood brain tumor.
- Circular RNAs (circRNAs) are implicated in the pathogenesis of various cancers, including MB.
Purpose of the Study:
- To investigate the role and mechanism of circRNA spindle and kinetochore associated complex subunit 3 (circ-SKA3) in medulloblastoma progression.
Main Methods:
- Quantitative real-time PCR was used to detect circ-SKA3 expression in MB tissues and cells.
- Functional assays (proliferation, migration, invasion, apoptosis, cell cycle) and in vivo xenograft models were employed to assess the effects of circ-SKA3.
- Mechanism was elucidated through RNA immunoprecipitation, luciferase reporter assays, and rescue experiments.
Main Results:
- Circ-SKA3 expression was significantly upregulated in MB tissues and cells.
- Circ-SKA3 knockdown suppressed MB cell proliferation, migration, and invasion, while inducing apoptosis and cell cycle arrest, and inhibited tumor growth in vivo.
- Circ-SKA3 acts as a molecular sponge for miR-326, leading to increased ID3 expression, which drives MB progression.
Conclusions:
- Circ-SKA3 functions as an oncogene in medulloblastoma by upregulating ID3 expression through sponging miR-326.
- Circ-SKA3 represents a potential therapeutic target for medulloblastoma treatment.
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