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Published on: October 30, 2013
Bladder Cancer Growth is Inhibited by Upregulating CircFUT8 through the METTL14/FMR1 Signaling Pathway
Weifeng Yang1,2, Jinhui Zha3, Youjuan Tang4
1Department of Urology, Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China. weifeng.yang@uszh.org.cn.
Abstract:
Bladder cancer (BCa) is one of the most common malignancies worldwide. This study investigates the role of the N6-methyladenosine (m6A)/circRNA regulatory axis in BCa tumor growth and elucidates its underlying molecular mechanisms. A total of 15 paired BCa and adjacent non-tumor tissues were collected. CircFUT8 expression was found to be significantly downregulated in BCa tissues and exhibited a positive correlation with methyltransferase-like 14 (METTL14) levels. It could also undergo m6A methylation, its expression was significantly upregulated following METTL14 overexpression in both T24 and UM-UC-3 cells, and silencing circFUT8 counteracted the suppressive effects of METTL14 overexpression on BCa cell growth and migration. RNA immunoprecipitation (RIP) assays confirmed that circFUT8 interacted with fragile X mental retardation 1 (FMR1), and FMR1 overexpression enhanced circFUT8 expression, while FMR1 knockdown diminished the effects of circFUT8 overexpression. In mice, FMR1 overexpression led to elevated circFUT8 levels, reduced Ki67 expression and smaller tumor volumes, and these effects could be reversed following METTL14 knockdown. Collectively, these findings highlight the METTL14/FMR1 signaling axis could enhance circFUT8 expression to inhibit BCa cells growth and migration. CircFUT8 thus represents a promising target for therapeutic intervention and provides novel mechanistic insights into the epigenetic regulation of BCa progression.
Insights
This study reveals that the METTL14/FMR1 signaling pathway enhances circFUT8 expression, inhibiting bladder cancer (BCa) cell growth and migration. CircFUT8 emerges as a potential therapeutic target for BCa.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Bladder cancer (BCa) is a prevalent malignancy globally.
- Understanding the molecular mechanisms driving BCa progression is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of the N6-methyladenosine (m6A)/circRNA regulatory axis in BCa.
- To elucidate the underlying molecular mechanisms involving circFUT8, METTL14, and FMR1 in BCa.
Main Methods:
- Analysis of 15 paired BCa and adjacent non-tumor tissues.
- Cellular experiments involving gene overexpression and knockdown (METTL14, circFUT8, FMR1).
- RNA immunoprecipitation (RIP) assays and in vivo mouse models.
Main Results:
- CircFUT8 expression was downregulated in BCa tissues and correlated positively with METTL14 levels.
- METTL14 overexpression upregulated circFUT8, while circFUT8 silencing counteracted METTL14's effects on BCa cells.
- FMR1 interacted with circFUT8, with FMR1 overexpression enhancing circFUT8 levels and inhibiting tumor growth in mice.
Conclusions:
- The METTL14/FMR1 signaling axis promotes circFUT8 expression, thereby inhibiting BCa cell growth and migration.
- CircFUT8 represents a promising therapeutic target for bladder cancer.
- This study provides novel insights into the epigenetic regulation of BCa progression.
