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The potential regulatory relationship between hsa_circ_0000973 and MBOAT2 in hypertriglyceridemia with abnormal
Fengdan Wang1, Yixue Yang2, Xiaotong Li1
1Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No. 1163 Xinmin Street, Chaoyang District, Changchun 130021, P. R. China.
Insights
Abnormal glucose metabolism (AGM) patients with hypertriglyceridemia (HTG) show decreased hsa_circ_0000973 and MBOAT2. hsa_circ_0000973 is a potential biomarker for HTG in AGM, potentially regulating TG metabolism with MBOAT2.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Hypertriglyceridemia (HTG) is common in abnormal glucose metabolism (AGM) populations, increasing health risks.
- Preliminary research identified hsa_circ_0000973 and MBOAT2 as potential regulators of HTG in AGM patients.
Purpose of the Study:
- To investigate the role and mechanism of hsa_circ_0000973 and MBOAT2 in AGM-associated HTG.
- To evaluate hsa_circ_0000973 as a diagnostic biomarker for HTG in AGM patients.
Main Methods:
- RT-qPCR to measure expression levels of hsa_circ_0000973 and MBOAT2 in 142 AGM subjects.
- ROC analysis for diagnostic performance evaluation.
- siRNA-mediated knockdown of hsa_circ_0000973 or MBOAT2 in insulin-resistant HepG2 cells for functional validation.
Main Results:
- Both hsa_circ_0000973 and MBOAT2 were significantly downregulated in AGM patients with HTG and negatively correlated with serum TG levels.
- hsa_circ_0000973 demonstrated high diagnostic accuracy for HTG in AGM (AUC = 0.95).
- Knockdown of either hsa_circ_0000973 or MBOAT2 in HepG2-IR cells led to increased TG accumulation, altered glucose metabolism, reduced proliferation, and increased apoptosis, affecting lipid metabolism transcription factors.
Conclusions:
- hsa_circ_0000973 is a potential biomarker for identifying HTG in the AGM population.
- hsa_circ_0000973 may jointly regulate triglyceride metabolism with MBOAT2 in the context of AGM.
Abstract:
Hypertriglyceridemia (HTG) frequently occurs in population with abnormal glucose metabolism (AGM), exacerbating risk. In our preliminary researches, we have screened hsa_circ_0000973 and MBOAT2 as the possible regulatory elements of HTG in AGM patients. This study enrolled 142 AGM subjects (71 with HTG, 71 with normal triglycerides) to investigate the role and mechanism of the hsa_circ_0000973 and MBOAT2 in AGM-associated HTG. Expression levels of hsa_circ_0000973 and MBOAT2 were measured by RT-qPCR. Diagnostic performance was evaluated via ROC analysis. Functional validation was performed in an insulin-resistant (IR) HepG2 cell model following knockdown of hsa_circ_0000973 or MBOAT2 using siRNA. Cellular triglyceride (TG) content, glucose uptake, proliferation, apoptosis, and expression of lipid metabolism transcription factors (SREBP-1c, PPARα, PPARγ) were assessed. In the AGM population, expression of both hsa_circ_0000973 and MBOAT2 was significantly downregulated in the HTG group and negatively correlated with serum TG levels (P <0 .01). hsa_circ_0000973 exhibited high diagnostic accuracy for HTG in the AGM population (AUC = 0.95). In HepG2-IR cells, knockdown of hsa_circ_0000973 decreased MBOAT2 expression, increased cellular TG accumulation and residual glucose, inhibited proliferation, and promoted apoptosis. Similar phenotypes were observed upon MBOAT2 knockdown. Both knockdowns upregulated SREBP-1c and downregulated PPARα and PPARγ. This study identified that hsa_circ_0000973 may serve as a candidate biomarker for identifying HTG specifically within the AGM population. Our in vitro experiments further suggested that, in the setting of AGM, hsa_circ_0000973 may jointly regulated TG metabolism alongside MBOAT2.
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