更新于：2024-09-19

FAM83A

更新于：2024-09-19

基本信息

别名

BJ-TSA-9、FAM83A、family with sequence similarity 83 member A

+ [5]

简介

Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both RAS/MAPK and PI3K/AKT/TOR signaling cascades downstream of EGFR. Required for the RAS/MAPK signaling cascade activation upon EGFR stimulation, it also activates both signaling cascades independently of EGFR activation.

关联

100 项与 FAM83A 相关的临床结果

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100 项与 FAM83A 相关的转化医学

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0 项与 FAM83A 相关的专利（医药）

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100

项与 FAM83A 相关的文献（医药）

2024-06-01·Journal for ImmunoTherapy of Cancer

High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC)

Article

作者: Angelakis, Athanasios ; Gavrielatou, Niki ; Moutafi, Myrto K ; Bates, Katherine M ; Rimm, David L ; Xirou, Vasiliki ; Aung, Thazin Nwe ; Milian, Rolando Garcia ; Salichos, Leonidas ; Vathiotis, Ioannis A ; Schalper, Kurt A

BackgroundDespite the impressive outcomes with immune checkpoint inhibitor (ICI) in non-small cell lung cancer (NSCLC), only a minority of the patients show long-term benefits from ICI. In this study, we used retrospective cohorts of ICI treated patients with NSCLC to discover and validate spatially resolved protein markers associated with resistance to programmed cell death protein-1 (PD-1) axis inhibition.MethodsPretreatment samples from 56 patients with NSCLC treated with ICI were collected and analyzed in a tissue microarray (TMA) format in including four different tumor regions per patient using the GeoMx platform for spatially informed transcriptomics. 34 patients had assessable tissue with tumor compartment in all 4 TMA spots, 22 with leukocyte compartment and 12 with CD68 compartment. The patients’ tissue that was not assessable in fourfold redundancy in each compartment was designated as the validation cohort; cytokeratin (CK) (N=22), leukocytes CD45 (N=31), macrophages, CD68 (N=43). The human whole transcriptome, represented by~18,000 individual genes assessed by oligonucleotide-tagged in situ hybridization, was sequenced on the NovaSeq platform to quantify the RNAs present in each region of interest.Results54,000 gene variables were generated per case, from them 25,740 were analyzed after removing targets with expression lower than a prespecified frequency. Cox proportional-hazards model analysis was performed for overall and progression-free survival (OS, PFS, respectively). After identifying genes significantly associated with limited survival benefit (HR>1)/progression per spot per patient, we used the intersection of them across the four TMA spots per patient. This resulted in a list of 12 genes in the tumor-cell compartment (RPL13A, GNL3, FAM83A, CYBA, ACSL4, SLC25A6, EPAS1, RPL5, APOL1, HSPD1, RPS4Y1, ADI1). RPL13A, GNL3in tumor-cell compartment were also significantly associated with OS and PFS, respectively, in the validation cohort (CK: HR, 2.48; p=0.02 and HR, 5.33; p=0.04). In CD45 compartment, secreted frizzled-related protein 2, was associated with OS in the discovery cohort but not in the validation cohort. Similarly, in the CD68 compartmentARHGAPand PNN interacting serine and arginine rich protein were significantly associated with PFS and OS, respectively, in the majority but not all four spots per patient.ConclusionThis work highlightsRPL13AandGNL3as potential indicative biomarkers of resistance to PD-1 axis blockade that might help to improve precision immunotherapy strategies for lung cancer.

2024-06-01·Cancer Medicine

Integrated whole‐exome and bulk transcriptome sequencing delineates the dynamic evolution from preneoplasia to invasive lung adenocarcinoma featured with ground‐glass nodules

Article

作者: Zhang, Jiao ; Zheng, Hong ; Deng, Xu-Feng ; Dai, Ji-Gang ; Zhou, Dong ; Li, Man-Yuan ; Li, Yan-Qi ; Liu, Quan-Xing ; Lu, Xiao ; Chen, Liang

AbstractObjectiveThe genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) remains unclear and requires further elucidation. We aimed to characterize gene mutations and expression landscapes, and explore the association between differentially expressed genes (DEGs) and significantly mutated genes (SMGs) during the dynamic evolution from AIS to IAC.MethodsThirty‐five patients with ground‐glass nodules (GGNs) lung adenocarcinomas were enrolled. Whole‐exome sequencing (WES) and transcriptome sequencing (RNA‐Seq) were conducted on all patients, encompassing both tumor samples and corresponding noncancerous tissues. Data obtained from WES and RNA‐Seq were subsequently analyzed.ResultsThe findings from WES delineated that the predominant mutations were observed in EGFR (49%) and ANKRD36C (17%). SMGs, including EGFR and RBM10, were associated with the dynamic evolution from AIS to IAC. Meanwhile, DEGs, including GPR143, CCR9, ADAMTS16, and others were associated with the entire process of invasive LUAD. We found that the signaling pathways related to cell migration and invasion were upregulated, and the signaling pathways of angiogenesis were downregulated across the pathological stages. Furthermore, we found that the messenger RNA (mRNA) levels of FAM83A, MAL2, DEPTOR, and others were significantly correlated with CNVs. Gene set enrichment analysis (GSEA) showed that heme metabolism and cholesterol homeostasis pathways were significantly upregulated in patients with EGFR/RBM10 co‐mutations, and these patients may have poorer overall survival than those with EGFR mutations. Based on the six calculation methods for the immune infiltration score, NK/CD8+ T cells decreased, and Treg/B cells increased with the progression of early LUAD.ConclusionsOur findings offer valuable insights into the unique genomic and molecular features of LUAD, facilitating the identification and advancement of precision medicine strategies targeting the invasive progression of LUAD from AIS to IAC.

2024-04-05·Mediators of Inflammation

Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction

Article

作者: Peng, Jing ; Tang, Hui ; Zhang, Xian ; Yang, Weitao ; Li, Hanmei ; Li, Dan

Objective. Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR. Methods. In this study, 11 healthy pregnant women and nine pregnant women with FGR were divided into Control group and FGR group based on the health status. Umbilical cord blood, maternal serum, feces, and placental tissue samples were collected during delivery. RNA sequencing, 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in umbilical cord blood circulating mRNA, fecal microbiota, and metabolites. RT-qPCR, ELISA, or western blot were used to detect the expression of top 5 differential circulating mRNA in neonatal cord blood, maternal serum, or placental tissue samples. Correlation between differential circulating mRNA, microbiota, and metabolites was analyzed by the Spearman coefficient. Results. The top 5 mRNA genes in FGR were altered with the downregulation of TRIM34, DEFA3, DEFA1B, DEFA1, and QPC, and the upregulation of CHPT1, SMOX, FAM83A, GDF15, and NAPG in newborn umbilical cord blood, maternal serum, and placental tissue. The abundance of Bacteroides, Akkermansia, Eubacterium_coprostanoligenes_group, Phascolarctobacterium, Parasutterella, Odoribacter, Lachnospiraceae_UCG_010, and Dielma were significantly enriched in the FGR group. Metabolites such as aspartic acid, methionine, alanine, L-tryptophan, 3-methyl-2-oxovalerate, and ketoleucine showed notable functional alterations. Spearman correlation analysis indicated that metabolites like methionine and alanine, microbiota (Tyzzerella), and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) might play a role as mediators in the communication between the gut and circulatory system interaction in FGR. Conclusion. Metabolites (METHIONINE, alanine) as well as microbiota (Tyzzerella) and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) were possible mediators that communicated the interaction between the gut and circulatory systems in FGR.

项与 FAM83A 相关的新闻（医药）

2023-02-24

·生物谷

STTT：唐景峰/汪振天团队合作揭示胰腺癌发展新机制，并开发潜在治疗短肽

研究团队还在FAM83A基因启动子区找到Wnt/β-catenin通路典型的TBE结合位点（TCF/LEF binding elements）。当Wnt3a刺激后，TCF4、β-catenin在该位点胰腺导管腺癌（PDAC）是一种预后极差的恶性肿瘤，5年生存率<5%。由于胰腺癌缺乏特异性的症状，而且病程早期就容易发生血管侵犯或远处转移，85%的病人初诊时即为晚期，仅有10-15%的病人能够获得手术机会。即使得到早期治疗，并且经过手术切除，仍有许多病人在术后出现局部或远处的复发和转移。加之胰腺癌对现有的治疗手段如放化疗等均不敏感且存在很强的耐药性。因此，明确与胰腺癌发生密切相关的基因表达及其参与的关键分子事件，对研究胰腺癌的发病机制及发现有效的治疗靶点具有重要的临床意义。近日，湖北工业大学细胞调控与分子药物“111”引智基地唐景峰课题组与复旦大学基础医学院汪振天课题组合作，在 Signal Transduction and Targeted Therapy 期刊发表了题为：B-lymphoid tyrosine kinase mediated FAM83A phosphorylation elevates pancreatic tumorigenesis through interacting with β-catenin 的研究论文。该论文聚焦胰腺癌发展过程中Wnt/β-catenin信号通路的调节机制，筛选并得到了一系列靶向FAM83A-β-catenin相互作用的阻断短肽，并充分验证了这类短肽在针对胰腺癌治疗中的转化前景。胰腺癌的形成主要是由一系列基因突变的积累及多条信号通路异常协同作用导致。从胰腺上皮细胞瘤样病变不典型增生（PanIN-1和PanIN-2）发展到原位癌（PanIN-3），最后形成具有侵袭性的肿瘤，这整个过程除了包含了前期原癌基因Kras的激活突变，中后期抑癌基因CDKN2A（编码INK4A抑制剂）、TP53 的失活突变和SMAD4/DPC4的基因丢失等之外，还伴随着Wnt/β-catenin等多条信号通路的异常激活。Wnt/β-catenin信号通路在调节细胞自我更新、细胞增殖、分化与凋亡、胚胎发育、组织稳态及细胞癌变等方面均发挥着重要的作用。各种致癌因素或者原癌基因导致的经典Wnt/β-catenin通路中的相关靶基因过表达，会致使游离的β-catenin在细胞内大量聚集，并通过核转位现象入核，与转录因子T细胞因子/淋巴增强因子复合物（TCF/LEF）结合，激活Wnt/β-catenin 信号转导通路的下游相关靶基因Cyclin D1、C-myc等的异常转录，调控基因表达，影响细胞的正常分化和发育，最终导致细胞癌变图1：FAM83A与β-catenin直接结合，并抑制降解复合体的组装，从而抑制β-catenin的磷酸化和降解该研究鉴定了一种新的具备核质分布的β-catenin相互作用蛋白FAM83A，并证明了FAM83A是Wnt/β-catenin信号通路的正向调节因子。同时，研究团队阐明了FAM83A调控Wnt通路的两种机制： 1）细胞质中，FAM83A能够作用并抑制β-catenin降解复合体的组装，从而抑制β-catenin与β-TrCP的结合，进而调控β-catenin蛋白的磷酸化和降解。在此基础上进一步发现FAM83A蛋白中DUF1669结构域介导该相互作用，并发现该结构域上的酪氨酸138残基（Y138）能够被SRC非受体激酶家族成员BLK激酶磷酸化。此外，FAM83A酪氨酸138磷酸化能够强化其在细胞质中的功能；图2：BLK磷酸化FAM83A Y138残基，磷酸化的FAM83A抑制β-连环蛋白破坏复合体组装和TCF4对HDAC的招募。此外，研究团队还在FAM83A基因启动子区找到Wnt/β-catenin通路典型的TBE结合位点（TCF/LEF binding elements）。当Wnt3a刺激后，TCF4、β-catenin在该位点的富集明显增多，FAM83A的表达水平明显提高，证明了FAM83A是Wnt/β-catenin信号通路的直接下游靶点，与Wnt/β-catenin信号通路形成一种正向调节回路。图3：靶向FAM83A-β-catenin相互作用的抑制肽在体内外均能显著抑制胰腺癌的生长和转移值得关注的是，研究团队根据FAM83A与β-catenin特异性相互作用结构区间，设计并筛选了一系列能够靶向该互作的关键阻断短肽，同时也在细胞、小鼠和斑马鱼模型中证明了其对胰腺癌生长、迁移和侵袭能力的抑制作用。也表明了针对胰腺癌中Wnt通路调控的短肽类药物在胰腺癌治疗中的转化应用前景。湖北工业大学青年教师周策凡副教授为论文第一作者，硕士生朱霄婷、刘南茜为共同第一作者，唐景峰与汪振天为论文共同通讯作者。该研究得到课题组国家自然科学基金项目(32070726、82273970、32270768、31871176、82173043)、湖北省杰出青年基金项目(2020CFA073)、武汉市科技计划项目(2019020701011475)资助。