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Published on: March 30, 2019
Long Noncoding RNA MAGI2-AS3 Represses Cell Progression in Clear Cell Renal Cell Carcinoma by Modulating the
Chengquan Yan1, Pengfei Wang1, Chaofei Zhao1
1Department of Urology, Area 3, Tangshan Gongren Hospital, Tangshan City, Hebei Province, 063000, China.
Abstract:
The objective of this study was to determine the regulatory mechanism of MAGI2-AS3 in clear cell renal cell carcinoma (ccRCC), thereby supplying a new insight for ccRCC treatment. Expression data in TCGA-KIRC were obtained. Target gene lncRNA for research was determined using expression analysis and clinical analysis. lncRNA's downstream regulatory miRNA and mRNA were predicted by bioinformatics databases. ccRCC cell malignant phenotypes were detected via CCK-8, colony formation, Transwell migration, and invasion assays. The targeting relationship between genes was assessed through dual-luciferase reporter gene analysis. Kaplan-Meier (K-M) analysis was carried out to verify the effect of MAGI2-AS3, miR-629-5p, and PRDM16 on the survival rate of ccRCC patients. MAGI2-AS3 expression in ccRCC tissue and cells was shown to be markedly decreased and its expression to continuously decline with tumor progression. MAGI2-AS3 suppresses ccRCC proliferation and migration. Dual-luciferase assay showed that MAGI2-AS3 binds miR-629-5p and that miR-629-5p binds PRDM16. In addition, functional experiments showed that MAGI2-AS3 facilitates PRDM16 expression by repressing miR-629-5p expression, thereby suppressing ccRCC cell aggression. K-M analysis showed that upregulation of either MAGI2-AS3 or PRDM16 significantly improves ccRCC patient survival, while upregulation of miR-629-5p has no significant impact. MAGI2-AS3 sponges miR-629-5p to modulate PRDM16 to mediate ccRCC development. Meanwhile, the MAGI2-AS3/miR-629-5p/PRDM16 axis, as a regulatory pathway of ccRCC progression, may be a possible therapeutic target and prognostic indicator of ccRCC.
Insights
MAGI2-AS3, a long non-coding RNA, is decreased in clear cell renal cell carcinoma (ccRCC). It suppresses ccRCC progression by regulating miR-629-5p and PRDM16, offering a potential therapeutic target for ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is a prevalent kidney cancer subtype.
- Understanding the molecular mechanisms underlying ccRCC progression is crucial for developing effective treatments.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
Purpose of the Study:
- To elucidate the regulatory mechanism of MAGI2-AS3 in clear cell renal cell carcinoma (ccRCC).
- To investigate the potential of MAGI2-AS3 as a therapeutic target and prognostic indicator for ccRCC.
Main Methods:
- Analysis of expression data from The Cancer Genome Atlas (TCGA-KIRC).
- Bioinformatic prediction of lncRNA targets (miRNA and mRNA).
- In vitro assays (CCK-8, colony formation, Transwell migration, invasion) to assess ccRCC cell phenotypes.
- Dual-luciferase reporter gene assays to confirm gene targeting relationships.
- Kaplan-Meier (K-M) analysis for survival rate assessment.
Main Results:
- MAGI2-AS3 expression is significantly decreased in ccRCC tissues and cells, correlating with tumor progression.
- MAGI2-AS3 suppresses ccRCC cell proliferation, migration, and invasion.
- MAGI2-AS3 directly binds to miR-629-5p, which in turn targets PRDM16.
- MAGI2-AS3 upregulates PRDM16 by inhibiting miR-629-5p, thereby suppressing ccRCC aggressiveness.
- High expression of MAGI2-AS3 or PRDM16 is associated with improved ccRCC patient survival.
Conclusions:
- MAGI2-AS3 acts as a tumor suppressor in ccRCC by sponging miR-629-5p and modulating PRDM16 expression.
- The MAGI2-AS3/miR-629-5p/PRDM16 axis represents a novel regulatory pathway in ccRCC progression.
- This axis holds promise as a potential therapeutic target and prognostic biomarker for ccRCC.
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