Background: Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal tumor and has become an important global health problem. The PI3K/AKT signaling pathway plays a key role in the development of ESCC. CircRNAs have been reported to be involved in the regulation of the PI3K/AKT pathway, but the underlying mechanisms are unclear. Therefore, this study aimed to identify protein-coding circRNAs and investigate their functions in ESCC.
Methods: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. Thereafter, LC-MS/MS was used to identify circPDE5A-encoded novel protein PDE5A-500aa. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circPDE5A and PDE5A-500aa in ESCC. Lastly, circRNA-loaded nanoplatforms were constructed to investigate the therapeutic translation value of circPDE5A.
Results: We found that circPDE5A expression was down-regulated in ESCC cells and tissues and that it was negatively associated with advanced clinicopathological stages and poorer prognosis in ESCC. Functionally, circPDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding PDE5A-500aa, a key regulator of the PI3K/AKT signaling pathway in ESCC. Mechanistically, PDE5A-500aa interacted with PIK3IP1 and promoted USP14-mediated de-ubiquitination of the k48-linked polyubiquitin chain at its K198 residue, thereby attenuating the PI3K/AKT pathway in ESCC. In addition, Meo-PEG-S-S-PLGA-based reduction-responsive nanoplatforms loaded with circPDE5A and PDE5A-500aa plasmids were found to successfully inhibit the growth and metastasis of ESCC in vitro and in vivo.
Conclusion: The novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of ESCC by promoting USP14-mediated de-ubiquitination of PIK3IP1 and may serve as a potential target for the development of therapeutic agents.
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http://dx.doi.org/10.1186/s13046-024-03054-3 | DOI Listing |
J Ethnopharmacol
December 2024
School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China. Electronic address:
Ethnopharmacological Relevance: Lichong decoction (LD) is extensively employed in the treatment of uterine leiomyoma (ULM), demonstrating remarkable clinical effectiveness with an absence of notable adverse reactions. Its composition aligns with the traditional Chinese medicine (TCM) etiology of ULM, making it a highly suitable therapy. Nonetheless, the precise mechanisms underlying its therapeutic actions remain to be fully elucidated.
View Article and Find Full Text PDFCell Signal
December 2024
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan 750021, China; School of Life Sciences, Ningxia University, Yinchuan 750021, China. Electronic address:
Objective: Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disease that entails dysregulated ovulation, hyperandrogenism, and polycystic ovaries. While Wnt5a has been suggested to play key roles in follicular development and female fertility under normal conditions, its functions in the context of PCOS have yet to be established. This study was thus designed to explore the impact of Wnt5a on ovarian granulosa cell autophagy in PCOS, providing in vitro evidence in support of its role in this setting.
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December 2024
Hepatology Diagnosis and Treatment Center & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China. Electronic address:
Cuproptosis is crucial in the development of various liver diseases, yet its involvement in alcoholic liver disease (ALD) remains poorly understood. In this study, we screened cuproptosis-related genes (CRGs) regulating ALD and explored their potential molecular mechanisms. Bioinformatic methods were employed to screen CRGs in ALD, analyze their functional enrichment, signaling pathways, transcriptional regulation, relationship with the immune microenvironment and pathogenic genes, and corresponding single nucleotide polymorphism pathogenic regions, and construct transcription factor-miRNA-mRNA networks.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
Sinopharm Group Guangdong Medi-World Pharmaceutical Co., Ltd., Guangzhou, China.
Immune injury is the main side effect caused by cyclophosphamide and the disruption of the intestinal barrier may be an important cause. Yupingfeng granules have been reported to have immunomodulatory effects and polysaccharides are important components of them. This study aimed to investigate the ameliorative effect of polysaccharides from Yupingfeng granules (YPFP) on cyclophosphamide induced immune injury and reveal their potential mechanisms based on its protective effect on the intestine.
View Article and Find Full Text PDFInflammation
December 2024
College of Pharmacy, Dali University, Dali, 671000, China.
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