{"title":"Mapping subcellular RNA localization with proximity labeling.","authors":"Jiapeng Liu, Binglin Zhong, Shuojun Li, Shuo Han","doi":"10.3724/abbs.2024147","DOIUrl":"https://doi.org/10.3724/abbs.2024147","url":null,"abstract":"<p><p>The subcellular localization of RNA is critical to a variety of physiological and pathological processes. Dissecting the spatiotemporal regulation of the transcriptome is key to understanding cell function and fate. However, it remains challenging to effectively enrich and catalogue RNAs from various subcellular structures using traditional approaches. In recent years, proximity labeling has emerged as an alternative strategy for efficient isolation and purification of RNA from these intricate subcellular compartments. This review focuses on examining RNA-related proximity labeling tools and exploring their application in elucidating the spatiotemporal regulation of RNA at the subcellular level.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huiling Nie, Yang Yu, Siqi Zhou, Yue Xu, Xi Chen, Xun Qin, Zhangyu Liu, Jiayu Huang, Hailiang Zhang, Jin Yao, Qin Jiang, Bingbing Wei, Xiaojian Qin
{"title":"TCF3 as a multidimensional biomarker: oncogenicity, genomic alterations, and immune landscape in pan-cancer analysis.","authors":"Huiling Nie, Yang Yu, Siqi Zhou, Yue Xu, Xi Chen, Xun Qin, Zhangyu Liu, Jiayu Huang, Hailiang Zhang, Jin Yao, Qin Jiang, Bingbing Wei, Xiaojian Qin","doi":"10.3724/abbs.2024126","DOIUrl":"https://doi.org/10.3724/abbs.2024126","url":null,"abstract":"<p><p>Transcription factor 3 (TCF3), a pivotal member of the TCF/LEF family, plays a critical role in tumorigenesis. Nonetheless, its impact on the tumor microenvironment (TME) and cancer phenotypes remains elusive. We perform an exhaustive analysis of TCF3 expression, DNA variation profiles, prognostic implications, and associations with the TME and immunological aspects. This study is based on a large-scale pan-cancer cohort, encompassing over 17,000 cancer patients from multiple independent datasets, validated by <i>in vitro</i> assays. Our results show that TCF3/4/7 exhibits differential expression patterns between normal and tumor tissues across pan-cancer analyses. Mutational analysis of TCF3 across diverse cancer types reveals the highest alteration rates in biliary tract cancer. Additionally, mutations and single nucleotide variants in TCF3/4/7 are found to exert varied effects on patient prognosis. Importantly, TCF3 emerges as a robust predictor of survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors. Elevated TCF3 expression is correlated with more aggressive cancer subtypes, as validated by immunohistochemistry and diverse cohort data. Furthermore, TCF3 expression is positively correlated with intratumoral heterogeneity and angiogenesis. <i>In vitro</i> investigations demonstrate that TCF3 is involved in epithelial-mesenchymal transition, migration, invasion, and angiogenesis. These effects are likely mediated through the interaction of TCF3 with the NF-κB/MMP2 pathway, which is modulated by IL-17A in human uveal melanoma MUM2B cells. This study elucidates, for the first time, the significant associations of TCF3 with DNA variation profiles, prognostic outcomes, and the TME in multiple cancer contexts. TCF3 holds promise as a molecular marker for diagnosis and as a potential target for novel therapeutic strategies, particularly in uveal melanoma.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuexue Zhu, Xinyu Meng, Xinyao Du, Chenyang Zhao, Xinyu Ma, Yuanyuan Wen, Shijie Zhang, Bao Hou, Weiwei Cai, Bin Du, Zhijun Han, Fei Xu, Liying Qiu, Haijian Sun
{"title":"Vaccarin suppresses diabetic nephropathy through inhibiting the EGFR/ERK1/2 signaling pathway.","authors":"Xuexue Zhu, Xinyu Meng, Xinyao Du, Chenyang Zhao, Xinyu Ma, Yuanyuan Wen, Shijie Zhang, Bao Hou, Weiwei Cai, Bin Du, Zhijun Han, Fei Xu, Liying Qiu, Haijian Sun","doi":"10.3724/abbs.2024141","DOIUrl":"https://doi.org/10.3724/abbs.2024141","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is recognized as one of the primary causes of chronic kidney disease and end-stage renal disease. Vaccarin (VAC) confers favorable effects on cardiovascular and metabolic diseases, including type 2 diabetes mellitus (T2DM). Nonetheless, the potential role and mechanism of VAC in the etiology of DN have yet to be completely elucidated. In this study, a classical mouse model of T2DM is experimentally induced via a high-fat diet (HFD)/streptozocin (STZ) regimen. Renal histological changes are assessed via H&E staining. Masson staining and immunohistochemistry (IHC) are employed to assess renal fibrosis. RT-PCR is utilized to quantify the mRNA levels of renal fibrosis, oxidative stress and inflammation markers. The levels of malondialdehyde (MDA) and reactive oxygen species (ROS), as well as the content of glutathione peroxidase (GSH-Px), are measured. The protein expressions of collagen I, TGF-β1, α-SMA, E-cadherin, Nrf2, catalase, SOD3, SOD2, SOD1, p-ERK, p-EGFR (Y845), p-EGFR (Y1173), p-NFκB P65, t-ERK, t-EGFR and t-NFκB P65 are detected by western blot analysis. Our results reveal that VAC has a beneficial effect on DN mice by improving renal function and mitigating histological damage. This is achieved through its inhibition of renal fibrosis, inflammatory cytokine overproduction, and ROS generation. Moreover, VAC treatment effectively suppresses the process of epithelial-mesenchymal transition (EMT), a crucial characteristic of renal fibrosis, in high glucose (HG)-induced HK-2 cells. Network pharmacology analysis and molecular docking identify epidermal growth factor receptor (EGFR) as a potential target for VAC. Amino acid site mutations reveal that Lys-879, Ile-918, and Ala-920 of EGFR may mediate the direct binding of VAC to EGFR. In support of these findings, VAC reduces the phosphorylation levels of both EGFR and its downstream mediator, extracellular signal-regulated kinase 1/2 (ERK1/2), in diabetic kidneys and HG-treated HK-2 cells. Notably, blocking either EGFR or ERK1/2 yields renal benefits similar to those observed with VAC treatment. Therefore, this study reveals that VAC attenuates renal damage via inactivation of the EGFR/ERK1/2 signaling axis in T2DM patients.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Liu, Zhiyuan Chen, Zhaoxing Li, Xinya Zhao, Weigang Zhang, Ao Zhang, Longxing Wen, Xiaoming Wang, Shuying Zhou, Daohai Qian
{"title":"Hsp90α promotes chemoresistance in pancreatic cancer by regulating Keap1-Nrf2 axis and inhibiting ferroptosis.","authors":"Bin Liu, Zhiyuan Chen, Zhaoxing Li, Xinya Zhao, Weigang Zhang, Ao Zhang, Longxing Wen, Xiaoming Wang, Shuying Zhou, Daohai Qian","doi":"10.3724/abbs.2024138","DOIUrl":"https://doi.org/10.3724/abbs.2024138","url":null,"abstract":"<p><p>Chemoresistance is the primary reason for poor prognosis in patients with pancreatic cancer (PC). Recent studies have indicated that ferroptosis may improve chemoresistance, but the underlying mechanisms remain unclear. In this study, significant upregulation of heat shock protein 90α (Hsp90α) expression is detected in the peripheral blood and tissue samples of patients with chemoresistant PC. Further studies reveal that Hsp90α promotes the proliferation, migration, and invasion of a chemoresistant pancreatic cell line (Panc-1-gem) by suppressing ferroptosis. Hsp90α competitively binds to Kelch-like ECH-associated protein 1 (Keap1), liberating nuclear factor erythroid 2-related factor 2 (Nrf2) from Keap1 sequestration. Nrf2 subsequently translocates into the nucleus and activates the glutathione peroxidase 4 (GPX4) pathway, thereby suppressing ferroptosis. This process further worsens the chemoresistance of PC cells. This study provides valuable insight into potential molecular targets to overcome chemoresistance in PC. It sheds light on the intricate mechanisms linking Hsp90α and ferroptosis to chemoresistance in PC and provides a theoretical foundation for the development of novel therapeutic strategies.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qianqian Song, Xiaoqing Tai, Qianyu Ren, Aiming Ren
{"title":"Structure-based insights into fluorogenic RNA aptamers.","authors":"Qianqian Song, Xiaoqing Tai, Qianyu Ren, Aiming Ren","doi":"10.3724/abbs.2024142","DOIUrl":"https://doi.org/10.3724/abbs.2024142","url":null,"abstract":"<p><p>Fluorogenic RNA aptamers are <i>in vitro-</i>selected RNA molecules capable of binding to specific fluorophores, significantly increasing their intrinsic fluorescence. Over the past decade, the color palette of fluorescent RNA aptamers has greatly expanded. The emergence and development of these fluorogenic RNA aptamers has introduced a powerful approach for visualizing RNA localization and transport with high spatiotemporal resolution in live cells. To date, a variety of tertiary structures of fluorogenic RNA aptamers have been determined using X-ray crystallography or NMR spectroscopy. Many of these fluorogenic RNA aptamers feature base quadruples or base triples in their fluorophore-binding sites. This review summarizes the structure-based investigations of fluorogenic RNA aptamers, with a focus on their overall folds, ligand-binding pockets and fluorescence activation mechanisms. Additionally, the exploration of how structures guide rational optimization to enhance RNA visualization techniques is discussed.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glycosylation in aging and neurodegenerative diseases.","authors":"Weilong Zhang, Tian Chen, Huijuan Zhao, Shifang Ren","doi":"10.3724/abbs.2024136","DOIUrl":"https://doi.org/10.3724/abbs.2024136","url":null,"abstract":"<p><p>Aging, a complex biological process, involves the progressive decline of physiological functions across various systems, leading to increased susceptibility to neurodegenerative diseases. In society, demographic aging imposes significant economic and social burdens due to these conditions. This review specifically examines the association of protein glycosylation with aging and neurodegenerative diseases. Glycosylation, a critical post-translational modification, influences numerous aspects of protein function that are pivotal in aging and the pathophysiology of diseases such as Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. We highlight the alterations in glycosylation patterns observed during aging, their implications in the onset and progression of neurodegenerative diseases, and the potential of glycosylation profiles as biomarkers for early detection, prognosis, and monitoring of these age-associated conditions, and delve into the mechanisms of glycosylation. Furthermore, this review explores their role in regulating protein function and mediating critical biological interactions in these diseases. By examining the changes in glycosylation profiles associated with each part, this review underscores the potential of glycosylation research as a tool to enhance our understanding of aging and its related diseases.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring glyco-signatures and their clinical implications: a special issue focused on glycosylation studies.","authors":"Haojia Lu, Xing Chen","doi":"10.3724/abbs.2024143","DOIUrl":"10.3724/abbs.2024143","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunoglobulin G glycosylation and its alterations in aging-related diseases.","authors":"Yongqi Wu, Zhida Zhang, Lin Chen, Shisheng Sun","doi":"10.3724/abbs.2024137","DOIUrl":"10.3724/abbs.2024137","url":null,"abstract":"<p><p>Immunoglobulin G (IgG) is an important serum glycoprotein and a major component of antibodies. Glycans on IgG affect the binding of IgG to the Fc receptor or complement C1q, which in turn affects the biological activity and biological function of IgG. Altered glycosylation patterns on IgG emerge as important biomarkers in the aging process and age-related diseases. Key aging-related alterations observed in IgG glycosylation include reductions in galactosylation and sialylation, alongside increases in agalactosylation, and bisecting GlcNAc. Understanding the role of IgG glycosylation in aging-related diseases offers insights into disease mechanisms and provides opportunities for the development of diagnostic and therapeutic strategies. This review summarizes five aspects of IgG: an overview of IgG, IgG glycosylation, IgG glycosylation with inflammation mediation, IgG glycan changes with normal aging, as well as the relevance of IgG glycan changes to aging-related diseases. This review provides a reference for further investigation of the regulatory mechanisms of IgG glycosylation in aging-related diseases, as well as for evaluating the potential of IgG glycosylation changes as markers of aging and aging-related diseases.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yong Ji, Yang Wang, Jiacheng Zou, Guanghao Liu, Mingyu Xia, Jun Ren, Daorong Wang
{"title":"Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2.","authors":"Yong Ji, Yang Wang, Jiacheng Zou, Guanghao Liu, Mingyu Xia, Jun Ren, Daorong Wang","doi":"10.3724/abbs.2024117","DOIUrl":"https://doi.org/10.3724/abbs.2024117","url":null,"abstract":"<p><p>Aberrant DNA methylation patterns in the promoter region of <i>PLCG2</i> are associated with dysregulated signaling pathways and cellular functions. Its role in colorectal cancer cells is still unknown. In this study, qRT-PCR is used to measure <i>DNMT3B</i> expression in colorectal cancer. Western blot analysis and immunohistochemistry are used to analyze DNMT3B and PLCG2 protein levels in colorectal tissues and cell lines. Cell Counting Kit-8 (CCK-8) and colony formation assays are used to assess the proliferation of colorectal cancer cells. Methylation-specific PCR (MSP) and bisulfite-sequencing PCR (BSP) are used to measure DNA methylation level. Our results show that DNMT3B is overexpressed in colorectal cells in the TCGA datasets according to Kaplan-Meier plots. DNMT3B is significantly overexpressed in tumor tissues compared to that in adjacent nontumor tissues. Western blot analysis results demonstrate high expression of DNMT3B in tumor tissues. Compared to normal colonic epithelial cells, colorectal cancer cell lines exhibit elevated level of <i>PLCG2</i> methylation. Overexpression of PLCG2 effectively prevents the growth of colorectal cancer xenograft tumors <i>in vivo</i>. PLCG2 is identified as a key downstream regulatory protein of DNMT3B in colorectal cancer. DNMT3B inhibits <i>PLCG2</i> transcription through methylation of the <i>PLCG2</i> promoter region. DNMT3B controls colorectal cancer cell proliferation through PLCG2, which is useful for developing therapeutic approaches that target PLCG2 expression for the treatment of colorectal cancer.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiyi He, Yunfei Zhang, Zenghui Mao, Gang Liu, Lihua Huang, Xiaowen Liu, Yuyan Su, Xiaowei Xing
{"title":"SUN5, a testis-specific nuclear membrane protein, participates in recruitment and export of nuclear mRNA in spermatogenesis.","authors":"Xiyi He, Yunfei Zhang, Zenghui Mao, Gang Liu, Lihua Huang, Xiaowen Liu, Yuyan Su, Xiaowei Xing","doi":"10.3724/abbs.2024134","DOIUrl":"https://doi.org/10.3724/abbs.2024134","url":null,"abstract":"<p><p><i>SUN5</i>, a testis-specific gene, is associated with acephalic spermatozoa syndrome (ASS). Here, we demonstrate that Sun5 is involved in mRNA export. In <i>Sun5</i>-knockout mice ( <i>Sun</i>5 <sup>-/-</sup>), poly(A) <sup>+</sup> RNA accumulates in the nuclei of germ cells, leading to reduced sperm counts, decreased sperm motility and disrupted sperm head-to-tail junctions. Additionally, in the GC-2 germ cell line with RNA interference of <i>Sun5</i>, heterogeneous nuclear ribonucleoproteins (hnRNPs) and poly (A) <sup>+</sup> RNA (mainly mRNA) are retained in the nucleus. Further mechanistic studies reveal that Sun5 interacts with Nxf1 (nuclear RNA export factor 1) and nucleoporin 93 (Nup93). Interference with Nup93 inhibits mRNA export. Treatment with leptomycin B to block the CRM1 pathway indicates that Sun5 regulates mRNA export through an Nxf1-dependent pathway. In <i>Sun5</i> <sup>-/-</sup> mice, the binding of Nxf1 and Nup93 decreases due to loss of Sun5 function, and the process of submitting Nxf1-binding mRNPs to Nup93 is inhibited, resulting in abnormal spermatogenesis. Together, these data may elucidate a novel pathway for mRNA export in male germ cells.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}