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circFTO upregulates transforming growth factor-alpha through sponging miR-148a-3p to regulate high glucose-induced
Yan Huang1, Xueyao Li1, Lu Jiang1
1Department of Ophthalmology, The People's Hospital of Yubei District of Chongqing City, Chongqing, 401120, China.
Abstract:
Diabetic retinopathy (DR) is one of the most common retinal microvascular diseases in diabetic patients. Therefore, elucidating the underlying molecular mechanism of DR is of great significance for its clinical treatment. This study explores the effects of the upregulated circFTO in DR patients in terms of cell apoptosis and viability. Several molecular assays are employed to explore these molecular mechanistic aspects, such as luciferase reporter, RNA pull-down, RT-qPCR, Western blot, and ELISA assays. miR-148a-3p is downregulated in DR patients. The expression of circFTO promoted ARPE-19 cells apoptosis and inhibited proliferation, reflecting the regulatory effect of circFTO/miR-148a-3p on retinal epithelial cells injury. In addition, the absence of circFTO could reduce ARPE-19 cells injury caused by HG by inhibiting oxidative stress and inflammation. Further, the investigations at the molecular level showed that circFTO could regulate the level of miR-148a-3p and TGFA in vitro. As the molecular sponge of miR-148a-3p, circFTO regulated cell viability and apoptosis and promoted the progression of DR through regulating the expression of TGFA. Together, this study provides new targets and markers for early diagnosis and therapy of DR.
Insights
This study reveals that elevated circFTO expression exacerbates diabetic retinopathy (DR) by promoting retinal cell apoptosis and inhibiting proliferation. circFTO acts as a molecular sponge for miR-148a-3p, contributing to DR progression.
Area of Science:
- Ophthalmology
- Molecular Biology
- Endocrinology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss in diabetic individuals.
- Understanding the molecular mechanisms of DR is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of upregulated circFTO in diabetic retinopathy.
- To elucidate the molecular mechanisms underlying circFTO's effects on retinal epithelial cells.
Main Methods:
- Luciferase reporter assays
- RNA pull-down assays
- RT-qPCR
- Western blot
- ELISA
Main Results:
- circFTO expression was upregulated in DR patients and promoted ARPE-19 cell apoptosis while inhibiting proliferation.
- circFTO acted as a molecular sponge for miR-148a-3p, regulating TGFA expression.
- Absence of circFTO reduced high glucose-induced retinal cell injury by inhibiting oxidative stress and inflammation.
Conclusions:
- circFTO plays a significant role in DR progression by affecting retinal epithelial cell viability and apoptosis.
- The circFTO/miR-148a-3p/TGFA axis represents a potential therapeutic target for DR.
- circFTO may serve as a novel biomarker for early DR diagnosis and treatment.
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