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PSMD12 promotes non-small cell lung cancer progression through activating the Nrf2/TrxR1 pathway
Lv Junqi,Ma Shengmao,Wang Xiaowen,Dang Jifang,Ma Fuchun 한국유전학회 2024 Genes & Genomics Vol.46 No.3
Background Non-small cell lung cancer (NSCLC) contributes to the vast majority of cancer-related deaths. Proteasome 26S subunit, non-ATPase 12 (PSMD12), a subunit of 26S proteasome complex, is known to play the tumor-promoting role in several types of cancer but its function in NSCLC remains elusive. Objective To explore the role and underlying mechanisms of PSMD12 in NSCLC. Methods The PSMD12 expression in human normal lung epithelial cell line (BEAS-2B) and four NSCLC cell lines (A549, NCI-H1299, NCI-H1975, Calu-1) were determined by qRT-PCR and western blot. Malignant phenotypes of NSCLC cells were detected by CCK-8, EdU staining, immunofluorescence staining for E-cadherin, flow cytometry, and Transwell assays to assess cell viability, proliferation, epithelial-mesenchymal transition (EMT), apoptosis, migration and invasion. Dual luciferase assay was used to verify the regulatory role of transcription factor on the promoter. Results We identified the upregulation of PSMD12 in NSCLC tissues based on the GEO datasets, which further verified in NSCLC and BEAS-2B cell lines. PSMD12 knockdown significantly suppressed malignant behaviors of NSCLC cells, including cell growth, invasion, and migration, while PSMD12 overexpression presented the opposite effects. Interestingly, we found that PSMD12 upregulated the tumor-promoting factor TrxR1 mRNA expression. For its potential mechanisms, we demonstrated that PSMD12 elevated transcription factor Nrf2 protein level and promoted Nrf2 nuclear translocation. And Nrf2 further increased TrxR1 promoter activity and enhanced TrxR1 transcription. Meanwhile, we proved that TrxR1 overexpression erased the inhibitory effect of PSMD12 knockdown. Conclusion PSMD12 promotes NSCLC progression by activating the Nrf2/TrxR1 pathway, providing a novel prognostic and therapeutic target for NSCLC treatment.
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Opportunities and Challenges of in vitro Synthetic Biosystem for Terpenoids Production
Yang Liyang,Gong Qiang,Lv Jifang,Zhou Bangyuan,Li Guilan,Guo JianQuan 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.5
Terpenoids are a large variety of natural products with remarkable diverse biological functions, and have a wide range of applications in flavors, pharmaceuticals, biofuels, pigments, and so on. However, limited production of terpenoids from natural resources constrains their use of bulk commodity products. In vivo synthetic biosystem, harnessing living organisms to produce terpenoids, has been broadly used and in-depth reviewed for terpenoids production, which has inherent weaknesses, such as slow reaction rate, low product yield, toxic intermediates, and high separation cost. In vitro synthetic biosystem, harboring numerous enzymes and/or coenzymes assembled into an in vitro enzymatic bioreactions, can obviate part of problems associated with in vivo style. In this review, the general design of in vitro synthetic biosystem is presented with seven supporting examples: mevalonate, isoprene, limonene, pinene, farnesene, amorpha-4,11-diene and taxadiene. The efforts for the large-scale implementation of in vitro synthetic biosystem have been addressed to enzymes engineering, computational modeling and cofactors recycle. The review also discusses the challenges and solutions for the largescale implementation of in vitro synthetic biosystem around enzymes stability and cofactors recycle. This review may suggest in vitro synthetic biosystems become a realistic option for the production of diverse valuable terpenoids, even expand to other commodity chemicals.
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