更新于：2024-05-01

GPRC5A

G protein-coupled receptor class C group 5 member A

更新于：2024-05-01

基本信息

别名

G protein-coupled receptor class C group 5 member A、G protein-coupled receptor, class C, group 5, member A、G-protein coupled receptor family C group 5 member A

+ [11]

简介

Orphan receptor. Could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways. Functions as a negative modulator of EGFR signaling (By similarity). May act as a lung tumor suppressor (PubMed:18000218).

关联

100 项与 GPRC5A 相关的临床结果

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100 项与 GPRC5A 相关的转化医学

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0 项与 GPRC5A 相关的专利（医药）

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159

项与 GPRC5A 相关的文献（医药）

2024-02-22·Molecular biotechnology

Circ_0007351 Exerts an Oncogenic Role In Colorectal Cancer Depending on the Modulation of the miR-5195-3p/GPRC5A Cascade.

Article

作者: Aijun He ; Fangxin Liao ; Xiaohui Lin

Circular RNAs (circRNAs) exert critical functions in colorectal cancer development. In this work, we wanted to elucidate the functional role and regulatory mechanism of circ_0007351 in colorectal cancer. For quantification of circ_0007351, microRNA (miR)-5195-3p and G Protein-coupled receptor class C group 5 member A (GPRC5A), a qRT-PCR, immunoblotting or immunohistochemistry assay was performed. Effects of circ_0007351/miR-5195-3p/GPRC5A cascade were evaluated by determining cell viability, proliferation, colony formation, motility, and invasion. Relationships among variables were assessed by dual-luciferase reporter assay. Animal studies were performed to evaluate circ_0007351's function in the growth of xenograft tumors. Circ_0007351 was markedly up-regulated in colorectal cancer tissues and cells. Down-regulation of circ_0007351 hindered cell growth, migration and invasiveness. Also, circ_0007351 depletion exerted a suppressive function in colorectal cell xenograft growth in vivo. Mechanistically, circ_0007351 sponged miR-5195-3p to sequester miR-5195-3p. Reduction of available miR-5195-3p neutralized the effects of circ_0007351 down-regulation on cell phenotypes. MiR-5195-3p directly targeted and inhibited GPRC5A. Circ_0007351 regulated GPRC5A expression by sponging miR-5195-3p. Moreover, the effects of circ_0007351 down-regulation on cell functional phenotypes were due to in part the reduction of GPRC5A expression. Our findings show that circ_0007351 down-regulation impedes proliferation, motility, and invasiveness in colorectal cancer cells at least in part via the regulation of the miR-5195-3p/GPRC5A cascade, highlighting that circ_0007351 inhibition may have a potential therapeutic value for colorectal cancer.

2024-02-01·Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy

Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer.

Article

作者: Xueqi Ou ; Yeru Tan ; Jindong Xie ; Jingping Yuan ; Xinpei Deng ; Ruonan Shao ; Cailu Song ; Xi Cao ; Xiaoming Xie ; Rongfang He ; Yuehua Li ; Hailin Tang

AIMS:

This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of breast cancer.

METHODS:

Single-cell RNA transcriptomic analysis and bioinformatic analysis are used to screen relevant genes in breast cancer metastatic hepatic specimens. MeRIP, dual-luciferase analysis and bioinformation were used to detect m6A modulation. Mass spectrometry (MS), co-inmunoprecipitation (co-IP) and immunofluorescence colocalization were executed to explore the mechanism of GPRC5A in breast cancer cells.

RESULT:

GPRC5A was upregulated in triple-negative breast cancer (TNBC) and was associated with a poor prognosis. In vitro and in vivo experiments demonstrated that knockdown of GPRC5A alleviated metastasis and resistance to docetaxel in TNBC. Overexpression of GPRC5A had the opposite effects. The m6A methylation of GPRC5A mRNA was modulated by METTL3 and YTHDF1, which facilitates its translation. GPRC5A inhibited the ubiquitination-dependent degradation of LAMTOR1, resulting in the recruitment of mTORC1 to lysosomes and activating the mTORC1/p70s6k signaling pathway.

CONCLUSION:

METTL3/YTHDF1 axis up-regulates GPRC5A expression by m6A methylation. GPRC5A activates mTORC1/p70s6k signaling pathway by recruiting mTORC1 to lysosomes, consequently promotes docetaxel-resistance and liver metastasis.

2023-11-09·European journal of pharmacology

Evolving views on the first two ligands of the angiotensin II type 2 receptor. From putative antagonists to potential agonists?

Review

作者: Gerry T M Wagenaar ; Gert N Moll

The renin-angiotensin system is one of the most complex regulatory systems that controls multiple organ functions. One of its key components, angiotensin II (Ang II), stimulates two G-protein coupled class A receptors: the Ang II type 1 (AT1) receptor and the Ang II type 2 (AT2) receptor. While stimulation of the AT1 receptor causes G-protein-dependent signaling and arrestin recruitment, the AT2 receptor seems to have a constitutively active-like conformation and appears to act via G-protein-dependent and -independent pathways. Overstimulation of the AT1 receptor may lead to unwanted effects like inflammation and fibrosis. In contrast, stimulation of the AT2 receptor leads to opposite effects thus restoring the balance. However, the role of the AT2 receptor has become controversial due to beneficial effects of putative AT2 receptor antagonists. The two first synthetic AT2 receptor-selective ligands, peptide CGP42112 and small molecule PD123319, were initially both considered antagonists. CGP42112 was subsequently considered a partial agonist and it was recently demonstrated to be a full agonist. Based on the search-term PD123319 in Pubmed, 1652 studies have investigated putative AT2 receptor antagonist PD123319. Here, we put forward literature that shows beneficial effects of PD123319 alone, even at doses too low for antagonist efficacy. These beneficial effects appear compatible with agonist-like activity via the AT2 receptor. Taken together, a more consistent image of a therapeutic role of stimulated AT2 receptor emerges which may clarify current controversies.

项与 GPRC5A 相关的新闻（医药）

2023-12-04

·今日头条

战肠癌，破译癌转移“罪魁祸首”！中山大学最新发文

本文为转化医学网原创，转载请注明出处作者：Sophia 导读：转移是癌症死亡的主要原因。然而，原发性肿瘤中有哪些类型的异质性癌细胞以及它们如何转移到靶器官在很大程度上仍未被发现。近日，中山大学郑健、林东昕等在期刊《Gut》上发表题为“Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis”的研究论文，研究破译了原发性结直肠癌组织、结直肠癌肝和卵巢转移组织中异质性癌细胞的亚型，以及单细胞分辨率下器官特异性结直肠癌转移的特征。 https://gut-bmj-com.libproxy1.nus.edu.sg/content/early/2023/11/30/gutjnl-2023-330243 研究背景 01 结直肠癌（CRC）是世界上第三大最常见和致命的癌症。肿瘤转移占结直肠癌死亡的 90%，据报道 5 年生存率为 <20%。虽然结直肠癌最常见的转移部位是淋巴结、肝脏和肺，但一部分结直肠癌可以转移到骨骼和卵巢。结直肠癌的卵巢转移被认为是由恶性细胞通过腹水从浆膜表面扩散到腹膜腔直接定植的。在过去的五十年中，对各种类型癌症的研究表明，尽管肿瘤中存在许多异质性细胞，但只有某些类型的恶性细胞才能驱动复发和远处转移。然而，迄今为止，似乎还没有关于哪种亚型异质性结直肠癌细胞更适合远处转移的系统研究。单细胞RNA测序（scRNA-seq）可以解剖异质性肿瘤并破译细胞组成。最近的研究比较了原发性结直肠癌及其肝转移性结直肠癌（lCRC）微环境中的细胞组成，发现与原发性结直肠癌相比，某些免疫细胞亚型（如肿瘤相关巨噬细胞和周细胞）在lCRC中显著富集。另一项研究报告称，与原发性结直肠癌相比，lCRC 中未成熟浆细胞增加，但活化的 B 细胞减少。尽管这些研究表明了不同免疫特征在结直肠癌和l结直肠癌微环境中的重要性，但仍未揭示哪种恶性细胞亚型是转移罪魁祸首。此外，据我们所知，卵巢转移性结直肠癌（oCRC）的肿瘤微环境和细胞组成从未被探索过。研究进展 02 我们对 7 例远处转移的 CRC 患者的 29 份样本进行了 scRNA-seq，包括 8 例原发性 CRC、5 例 oCRC、2 例 lCRC、7 例邻近正常组织和 7 例外周血单核细胞（PBMC）。我们还下载了来自 24 名患者的 41 个样本的公开 scRNA-seq 数据，包括 29 个 CRC 和 12 个邻近正常组织，以增加统计功效。在这 24 例患者中，有 3 例有远处转移，但无法获得详细的转移信息。因此，在最终分析中，我们有 31 例 CRC 患者，包括 10 例远处转移。所有结直肠癌均被诊断为微卫星稳定型（MSS）结直肠癌。患者和组织样本的工作流程和详细信息如图1A所示。 CRC样本采集、scRNA-seq和空间转录组学分析的示意图，以及与公开数据集的联合分析我们对表达EPCAM和KRT18的上皮细胞进行了亚分类，发现所有患者都存在14种细胞亚型（图2A）。这14种细胞亚型的标记基因如图2B所示。在14种细胞亚型中，我们鉴定了5种恶性细胞亚型，包括高表达ASCL2和PTPRO的干细胞样细胞、表达DNAJB1和RND3的DNAJB1恶性细胞、表达FDPS和SCD的FDPS恶性细胞、表达GPRC5A和SLC2A1的GPRC5A恶性细胞以及表达IL32和S100A11的IL32恶性细胞（图2B）。我们发现肠细胞在正常结直肠组织中富集，胆管细胞在lCRC和干细胞样细胞中富集，其他恶性细胞亚型在原发性和转移性CRC样本中富集（图2C）。来自原发性结直肠癌和转移性结直肠癌的干细胞样恶性细胞亚型的DNA拷贝数变异明显高于邻近正常组织的上皮细胞（图2D-E）。然后，我们应用CytoTRACE14预测了5种恶性细胞亚型的分化状态，结果显示干细胞样细胞在lCRC或oCRC中具有明显高于其他细胞类型的分化潜力。基于分区的图抽象分析表明，与其他上皮细胞亚型相比，干细胞样细胞与恶性细胞亚型的进化关系更密切（图2F）。RNA速度分析表明，流动方向是从干细胞样细胞到其他恶性细胞亚型（图2F）。此外，在所有上皮细胞亚型中，干细胞样细胞具有最高的干性特征评分（图2G）。这些结果表明，干细胞样细胞可能是CRC转移的始作俑者。干细胞样细胞是结直肠癌转移的始作俑者研究结论 03 总之，通过使用整合scRNA-seq、空间转录组分析和功能测定，我们发现了一个以PTPRO和ASCL2为转移罪魁祸首的干细胞样细胞簇，其亚群显示出进一步不同的肝脏或卵巢器官趋性。在原发性结直肠癌中，转移的结直肠癌细胞通过NOTCH信号通路与CAF和D内皮细胞相互作用，为其转移获取营养和能量。我们的研究结果揭示了器官特异性CRC转移的转移罪魁祸首。此外，先前的研究报道了包括 LGR5 和 AXIN2 在内的 Wnt 靶基因是上皮组织中的功能性干细胞标志物，而 ASCL2 仅限于胃和肠道干细胞。Wang 等人表明，高水平的 ASCL2 表达对于维持胃 CSC 的自我更新特性和致癌性至关重要。因此，我们的发现也可能与其他胃肠道癌症有关，尤其是胃癌，这值得深入研究。参考资料： https://gut-bmj-com.libproxy1.nus.edu.sg/content/early/2023/11/30/gutjnl-2023-330243 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 北京｜12月19日-20日 ▶第四届单细胞测序技术应用研讨会暨单细胞&空间组学研讨会（日程稍后公布）点击对应文字查看详情

临床研究

2023-09-14

·生物谷

南方医科大学研究者们揭示了靶向EZH_005/hnRNPA1/Gprc5a轴可能是肠I/R损伤的潜在治疗策略

肠缺血/再灌注(I/R)是一种常见而严重的临床问题，可导致肠道损伤和多器官功能障碍，甚至衰竭。虽然急性肠缺血的死亡率和并发症发生率较高，但如果及时诊断和治疗，通常是可以逆转的。肠缺血/再灌注(I/R)是一种常见而严重的临床问题，可导致肠道损伤和多器官功能障碍，甚至衰竭。虽然急性肠缺血的死亡率和并发症发生率较高，但如果及时诊断和治疗，通常是可以逆转的。为了提高早期诊断，一些研究建议检测不同的生物标志物，包括肠道脂肪酸结合蛋白、二胺氧化酶、谷胱甘肽S转移酶、瓜氨酸和平滑肌蛋白。尽管大多数这些生物标志物在临床前研究中被证明是有价值的，但它们在临床环境中的使用受到几个缺点的限制，包括敏感性和特异性低以及可靠性和准确性差。因此，迫切需要更敏感、更特异的肠道损伤标志物。图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1038/s41467-023-41147-3 近日，来自南方医科大学的研究者们在Nature Communications杂志上发表了题为“Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating Gprc5a signaling”的文章，该研究揭示了肠损伤生物标志物胞外体EZH2_005通过介导Gprc5a信号转导减轻肠缺血再灌注损伤。肠缺血/再灌注(I/R)损伤是一种严重的临床疾病，缺乏理想的诊断标记物，也没有明确的分子病因。血浆外体环状RNA(CircRNAs)是多种疾病的重要生物标志物和治疗靶点，但其在肠I/R损伤中的作用尚不清楚。在本研究中，研究者筛选了从肠道I/R小鼠收集的肠道组织外切体中CircRNAs的表达谱，并鉴定CircEZH2_005是一个显著下调的外切体CircRNA。心脏手术后发生肠I/R损伤的临床心脏手术患者血浆中EZH2_005水平也降低。EZH2_005外切体对I/R所致的肠损伤具有重要的诊断价值。 CircEZH2_005上调通过与hnRNPA1直接相互作用促进Lgr5+干细胞的增殖，增强Gprc5a的稳定性，从而减轻I/R引起的肠粘膜损伤。EZH2_005可作为肠I/R损伤的生物标志物，靶向EZH_005/hnRNPA1/Gprc5a轴可能是肠I/R损伤的潜在治疗策略。 CircEZH2_005通过hnRNPA1调节Gprc5a稳定的机制示意图图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1038/s41467-023-41147-3 综上所述，本研究描述了一种与肠I/R损伤相关的CircRNA，称为CircEZH2_005，它在血浆外体中被可靠地检测到，并能有效地区分有肠I/R损伤的患者和无肠I/R损伤的患者。此外，EZH2_005通过与hnRNPA1直接相互作用促进隐窝干细胞的增殖，增强Gprc5a在肠I/R过程中的稳定性，从而减轻肠粘膜损伤。因此，本研究不仅为肠I/R损伤的早期检测提供了一种有前景的无创生物标志物，而且为抗肠I/R损伤的治疗策略开辟了一条途径。（生物谷 Bioon.com）参考文献 Wenjuan Zhang et al. Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating Gprc5a signaling. Nat Commun. 2023 Sep 6;14(1):5437. doi: 10.1038/s41467-023-41147-3.

核酸药物

2023-08-14

·BioSpace

GeneTex Addresses GPCR Targets With Its Recombinant Monoclonal Antibody Production Platform

IRVINE, CA / ACCESSWIRE / August 14, 2023 / GeneTex, a multinational antibody manufacturing company, is leveraging its recombinant monoclonal antibody production platform and augmented validation protocols to generate immunological reagents against high-value targets that have historically proven difficult to produce. G protein-coupled receptors (GPCRs), one of the most notoriously challenging groups, constitute the largest membrane protein superfamily in the human genome with more than 800 genes. These multipass membrane proteins are involved in a myriad of essential functions in normal physiology and in many diseases. Importantly, almost a third of therapeutics in use today are directed against GPCRs, and future drug development will benefit from well-validated antibodies against other GPCRs. Thus, the need for dependable antibodies to study these proteins among scientists in the academic, clinical, and pharmaceutical fields is critical. As noted above, the development of antibodies specific for individual GPCRs has proven to be technically difficult. Much of the GPCR structure is buried in the cell membrane. In addition, cell expression levels are often quite low for many GPCRs, and identifying an immunoreactive antigen that recapitulates the required conformational structure while also being specific for a particular GPCR can be elusive. Antibody specificity for the targeted GPCR and unambiguous demonstration of performance in experimental applications (e.g., western blot, immunohistochemistry, and immunocytochemistry) valued by researchers are equally formidable to establish. GeneTex is relying on the advantages of its recombinant antibody technology as well as enhanced validation strategies to surmount these obstacles. For production, the recombinant antibody workflow allows the detection of promising clones early in the process and scalability and consistency after the clones are selected. GeneTex's validation efforts will focus on CRISPR-based knockout (KO) protocols coupled with the implementation of VirDTM-GPCR arrays (developed by CDI Labs, Baltimore, MD), which present a nearly comprehensive library of human non-olfactory GPCRs individually expressed on virion envelopes. These arrays allow the most effective large-scale screening mechanism to test the specificity of any human GPCR-binding reagent. Scott Paschke, Vice President at CDI Labs, states, "We are excited to be working with GeneTex on their efforts to produce highly specific GPCR antibodies. CDI's GPCR VirDTM arrays are produced by a patented method that expresses the human GPCR protein through the use of an engineered HSV-1 virus. This system yields a recombinant human GPCR protein embedded in a human membrane to ensure correct folding. The VirDTM system is a perfect tool for assaying GPCR antibody specificity." These efforts by GeneTex have already produced new antibodies for two important GPCRs. The first is the new D2 dopamine receptor (DRD2) antibody (GTX636952) that targets one of the five GPCRs responsible for dopamine signaling in humans. DRD2 is particularly significant as the target of drugs used to treat psychoses and Parkinson's disease. GeneTex's recombinant antibody is validated using comparable antibodies, differential tissue expression, and the VirDTM-GPCR array in the process of affirming its use in several applications. The array data was remarkable for a distinct signal for DRD2 but not for DRD3, DRD5, or any other GPCR or membrane protein on the array, which argues that the antibody is specific for DRD2. A second recombinant antibody for retinoic acid-induced protein 3 (RAI3/GPRC5A) (GTX637589), which may be a prognostic marker for several major human malignancies, was validated using CRISPR KO, tissue staining, and differential cell line expression. These two reagents are just the first of what GeneTex hopes will be an extensive and highly refined catalog of GPCR antibodies to meet the needs of GPCR researchers. Allen Lee, GeneTex's Vice President of Business Development, commented, "Over the next two years, GeneTex will produce the most comprehensive portfolio of best-in-class antibodies against GPCRs. We hope this will accelerate drug discovery and research." Contact Information: Allen Lee Vice President - Business Development allensl@genetex.com (949) 553-1900 SOURCE: GeneTex, Inc. View source version on accesswire.com: