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2 results on '"Pinjia Liu"'

1. M6A-mediated upregulation of circMDK promotes tumorigenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

Author

Ashuai Du, Shiqin Li, Yuzheng Zhou, Cyrollah Disoma, Yujie Liao, Yongxing Zhang, Zongpeng Chen, Qinglong Yang, Pinjia Liu, Sixu Liu, Zijun Dong, Aroona Razzaq, Siyi Tao, Xuan Chen, Yuxin Liu, Lunan Xu, Qianjun Zhang, Shanni Li, Jian Peng, and Zanxian Xia

Subjects
Hepatocellular carcinoma (HCC), circRNA, N6-methyladenosine (m6A), IGF2BP1, ATG16L1, Apoptosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Emerging evidence suggest the critical role of circular RNAs (circRNAs) in disease development especially in various cancers. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) is still largely unknown. Methods RNA sequencing was performed to identify significantly upregulated circRNAs in paired HCC tissues and non-tumor tissues. CCK-8 assay, colony formation, transwell, and xenograft mouse models were used to investigate the role of circRNAs in HCC proliferation and metastasis. Small interfering RNA (siRNA) was used to silence gene expression. RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assay and western blot were used to explore the underlying molecular mechanisms. Results Hsa_circ_0095868, derived from exon 5 of the MDK gene (named circMDK), was identified as a new oncogenic circRNA that was significantly upregulated in HCC. The upregulation of circMDK was associated with the modification of N6-methyladenosine (m6A) and poor survival in HCC patients. Mechanistically, circMDK sponged miR-346 and miR-874-3p to upregulate ATG16L1 (Autophagy Related 16 Like 1), resulting to the activation of PI3K/AKT/mTOR signaling pathway to promote cell proliferation, migration and invasion. Poly (β-amino esters) (PAEs) were synthesized to assist the delivery of circMDK siRNA (PAE-siRNA), which effectively inhibited tumor progression without obvious adverse effects in four liver tumor models including subcutaneous, metastatic, orthotopic and patient-derived xenograft (PDX) models. Conclusions CircMDK could serve as a potential tumor biomarker that promotes the progression of HCC via the miR-346/874-3p-ATG16L1 axis. The PAE-based delivery of siRNA improved the stability and efficiency of siRNA targeting circMDK. The PAE-siRNA nanoparticles effectively inhibited HCC proliferation and metastasis in vivo. Our current findings offer a promising nanotherapeutic strategy for the treatment of HCC. Graphical Abstract

Published
2022
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2. Host E3 ligase HUWE1 attenuates the proapoptotic activity of the MERS-CoV accessory protein ORF3 by promoting its ubiquitin-dependent degradation

Author

Yuzheng Zhou, Rong Zheng, Sixu Liu, Cyrollah Disoma, Ashuai Du, Shiqin Li, Zongpeng Chen, Zijun Dong, Yongxing Zhang, Sijia Li, Pinjia Liu, Aroona Razzaq, Xuan Chen, Yujie Liao, Siyi Tao, Yuxin Liu, Lunan Xu, Qianjun Zhang, Jian Peng, Xu Deng, Shanni Li, Taijiao Jiang, and Zanxian Xia

Subjects
HUWE1, viruses, Ubiquitin-Protein Ligases, SARS-CoV, severe acute respiratory syndrome coronavirus, CQ, chloroquine, Apoptosis, Viral Nonstructural Proteins, ubiquitination, Biochemistry, KEGG, Kyoto Encyclopedia of Genes and Genomes, Cell Line, MERS-CoV, CHX, cycloheximide, M, membrane, Humans, IFN, interferon, Molecular Biology, degradation, Tumor Suppressor Proteins, virus diseases, Computational Biology, MERS-CoV, Middle East respiratory syndrome coronavirus, Epithelial Cells, Cell Biology, PROTAC, protein hydrolysis targeting chimera, ORF3, respiratory tract diseases, HEK293 Cells, A549 Cells, Host-Pathogen Interactions, BTM, bortezomib, Middle East Respiratory Syndrome Coronavirus, NSPs, nonstructural proteins, Coronavirus Infections, SARS-CoV-2, severe acute respiratory syndrome coronavirus-2, Research Article, N, nucleocapsid
Abstract

With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups: nonstructural proteins, structural proteins, and accessory proteins. While the number of each of these proteins varies greatly among different coronaviruses, accessory proteins are most closely related to the pathogenicity of the virus. We found for the first time that the ORF3 accessory protein of MERS-CoV, which closely resembles the ORF3a proteins of severe acute respiratory syndrome coronavirus and SARS-CoV-2, has the ability to induce apoptosis in cells in a dose-dependent manner. Through bioinformatics analysis and validation, we revealed that ORF3 is an unstable protein and has a shorter half-life in cells compared to that of severe acute respiratory syndrome coronavirus and SARS-CoV-2 ORF3a proteins. After screening, we identified a host E3 ligase, HUWE1, that specifically induces MERS-CoV ORF3 protein ubiquitination and degradation through the ubiquitin-proteasome system. This results in the diminished ability of ORF3 to induce apoptosis, which might partially explain the lower spread of MERS-CoV compared to other coronaviruses. In summary, this study reveals a pathological function of MERS-CoV ORF3 protein and identifies a potential host antiviral protein, HUWE1, with an ability to antagonize MERS-CoV pathogenesis by inducing ORF3 degradation, thus enriching our knowledge of the pathogenesis of MERS-CoV and suggesting new targets and strategies for clinical development of drugs for MERS-CoV treatment.

Published
2022

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