Familial partial lipodystrophy 3 (FPLD3) is a rare genetic disorder caused by loss-of-function mutations in the gene, characterized by a selective absence of subcutaneous fat and associated metabolic complications. However, the molecular mechanisms of FPLD3 remain unclear. In this study, we recruited a 17-yr-old Chinese female with FPLD3 and her family, identifying a novel frameshift mutation (exon 4: c.418dup: p.R140Kfs*7) that truncates the PPARγ protein at the seventh amino acid, significantly expanding the genetic landscape of FPLD3. By performing next-generation sequencing of circular RNAs (circRNAs), microRNAs (miRNAs), and mRNAs in plasma exosomes, we discovered 59 circRNAs, 57 miRNAs, and 299 mRNAs were significantly altered in the mutation carriers compared with the healthy controls. Integration analysis highlighted that the circ_0001597-miR-671-5p pair and 18 mRNAs might be incorporated into the metabolic regulatory networks of the FPLD3 induced by the novel mutation. Functional annotation suggested that these genes were significantly enriched in glucose- and lipid metabolism-related pathways. Among the circRNA-miRNA-mRNA network, we identified two critical regulators, early growth response-1 (), a key transcription factor known for its role in insulin signaling pathways and lipid metabolism, and 1-acylglycerol-3-phosphate -acyltransferase 3 (), which gets involved in the biosynthesis of triglycerides and lipolysis. Circ_0001597 regulates the expression of these genes through miR-671-5p, potentially contributing to the pathophysiology of FPLD3. Overall, this study clarified a circulating exosomal circRNA-miRNA-mRNA network in a FPLD3 family with a novel mutation, providing evidence for exploring promising biomarkers and developing novel therapeutic strategies for this rare genetic disorder. Through the establishment of a ceRNA regulatory networks in a novel frameshift mutation c.418dup-induced FPLD3 pedigree, this study reveals that circ_0001597 may contribute to the pathophysiology of FPLD3 by sequestering miR-671-5p to regulate the expression of and , pivotal genes situated in the triglyceride (TG) synthesis and lipolysis pathways. Current findings expand our molecular understanding of adipose tissue dysfunction, providing potential blood biomarkers and therapeutic avenues for lipodystrophy and associated metabolic complications.
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http://dx.doi.org/10.1152/ajpendo.00094.2024 | DOI Listing |
Health Inf Sci Syst
December 2025
Medical School, Kunming University of Science & Technology, #727 Jing Ming Nan Road, Chenggong County, Kunming, 650500 Yunnan China.
Background: Circular RNAs (circRNAs) are involved in the occurrence and development of various tumors. CircRNAs can act as competing endogenous RNAs (ceRNAs), which are important regulatory networks, by regulating microRNAs (miRNAs). However, the effects of ceRNA networks on lung cancer (LC), especially the circRNA-miRNA-mRNA regulatory network, remain incompletely understood.
View Article and Find Full Text PDFInt J Gen Med
December 2024
Department of Respiratory Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, People's Republic of China.
Background: Non-smoking women with lung adenocarcinoma(NSWLA) is a significant health problem globally; the carcinogenesis and prognostic signature remain poorly understood. Circular RNAs (circRNAs) are gradually implicated in cancer formation through sponging miRNAs to regulate mRNAs.
Methods: Tumor and paracancerous specimens from non-smoking women after lung adenocarcinoma surgery were collected for high-throughput sequencing of circRNA.
Virus Res
December 2024
Medical School, Kunming University of Science and Technology, Kunming, Yunnan Province, China. Electronic address:
Coxsackievirus B5 (CVB5) is a major pathogen responsible for hand-foot-mouth disease, herpangina, and even severe death. The mechanisms underlying CVB5-induced diseases are not fully elucidated, and no specific antiviral treatments are currently available. Circular RNAs (circRNAs), a closed-loop molecular structure, have been reported to be involved in virus infectious diseases.
View Article and Find Full Text PDFImmunotargets Ther
November 2024
Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, People's Republic of China.
Background: Sorafenib, an orally active potent tyrosine kinase inhibitor (TKI), represented a primary treatment in patients with advanced hepatocellular carcinoma (HCC). Unfortunately, sorafenib resistance was regarded as a huge obstacle for HCC treatment.
Methods: RNA-sequencing including circRNA Sequencing (circRNA-Seq) for circular RNAs (circRNAs), miRNA Sequencing (miRNA-Seq) for microRNAs (miRNAs), as well as mRNA Sequencing (mRNA-Seq) for mRNAs in , were performed.
J Inflamm Res
November 2024
Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230031, People's Republic of China.
Background: Wilson's disease (WD) is a hereditary disorder characterized by an abnormality in copper metabolism. Liver fibrosis, and potentially cirrhosis, induced by copper accumulation are critical factors in the pathogenesis of WD. CircRNAs exhibit high stability and play crucial roles in numerous biological processes.
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