P4ha3-flox 基因敲除小鼠

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产品名称

P4ha3-flox 基因敲除小鼠

产品编号

S-CKO-10441

品系全称

C57BL/6JCya-P4ha3em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-320452-P4ha3-B6J-VA

品系状态

使用本品系发表的文献需注明: P4ha3-flox 基因敲除小鼠 mice (Strain S-CKO-10441) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide III
基因别称
D930031A02Rik
染色体号
Chr 7 (Mouse)
转录本 ID
NCBI: NM_177161.4 | Ensembl: ENSMUST00000057023
修饰方式
条件性基因敲除
靶向范围
Exon 6~7
敲除长度
~1044 bp
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
P4HA3,也称为Prolyl-4-hydroxylase subunit alpha 3,是胶原合成中的一种关键酶,属于脯氨酰-4-羟化酶(P4Hs)家族。P4Hs家族成员在细胞外基质(ECM)的动态调控中发挥重要作用,而ECM的动态变化与肿瘤的发生、发展密切相关。P4HA3的表达和活性调节在多种肿瘤中发挥重要作用,包括肝胆管反应、胆管纤维化、肾细胞癌、结肠癌、头颈鳞状细胞癌、胃癌等。

在胆汁淤积性肝病中,P4HA2与肝胆管反应和胆管纤维化密切相关。在原发性胆管炎(PBC)和原发性硬化性胆管炎(PSC)患者中,P4HA2的表达水平显著升高。P4HA2的表达与肝损伤的严重程度呈正相关。在P4HA2敲除小鼠中,肝胆管反应和纤维化程度明显降低。这些研究表明,P4HA2通过调节SAV1介导的Hippo信号通路,促进肝胆管反应和胆管纤维化[1]。

在肾细胞癌中,P4HA3的表达水平显著升高,与患者的预后不良相关。P4HA3的表达与肿瘤的增殖、侵袭和转移能力密切相关。P4HA3通过调节PI3K/AKT/GSK3β信号通路,促进肾细胞癌的进展。P4HA3的敲低可以抑制肾细胞癌细胞的增殖、迁移和侵袭能力,表明P4HA3是肾细胞癌的潜在治疗靶点[2]。

在结肠癌中,P4HA3的表达水平也显著升高,与淋巴转移、Dukes分期和患者生存率密切相关。P4HA3的表达与巨噬细胞浸润水平呈正相关。P4HA3的敲低可以促进巨噬细胞对结肠癌细胞的吞噬,而P4HA3的过表达则抑制巨噬细胞的吞噬能力。P4HA3通过上调CD47的表达,使结肠癌细胞逃避巨噬细胞的吞噬。此外,P4HA3还促进IL34和M-CSF的分泌,进一步促进巨噬细胞向M2型分化,从而促进结肠癌的进展[3]。

P4HA3的表达与多种肿瘤的预后相关,包括肝胆管反应、胆管纤维化、肾细胞癌、结肠癌、头颈鳞状细胞癌、胃癌等。P4HA3的表达与肿瘤的增殖、侵袭和转移能力密切相关。P4HA3通过调节多种信号通路,如Hippo信号通路、PI3K/AKT/GSK3β信号通路、TGF-β/Smad信号通路等,促进肿瘤的进展。P4HA3的表达与免疫浸润相关,表明P4HA3可能成为肿瘤免疫治疗的潜在靶点。

综上所述,P4HA3在多种肿瘤的发生、发展中发挥重要作用。P4HA3的表达和活性调节与肿瘤的预后相关。P4HA3通过调节多种信号通路,促进肿瘤的进展。P4HA3的表达与免疫浸润相关,表明P4HA3可能成为肿瘤免疫治疗的潜在靶点。P4HA3的研究有助于深入理解肿瘤的发生、发展机制,为肿瘤的治疗和预防提供新的思路和策略[4,5,6,7,8,9,10]。

参考文献:
1. Zhang, Jun, Lyu, Zhuwan, Li, Bo, Xiao, Xiao, Ma, Xiong. 2023. P4HA2 induces hepatic ductular reaction and biliary fibrosis in chronic cholestatic liver diseases. In Hepatology (Baltimore, Md.), 78, 10-25. doi:10.1097/HEP.0000000000000317. https://pubmed.ncbi.nlm.nih.gov/36799463/
2. Zhang, Zhechuan, Zhang, Yuanfeng, Zhang, Ronggui. 2023. P4HA3 promotes clear cell renal cell carcinoma progression via the PI3K/AKT/GSK3β pathway. In Medical oncology (Northwood, London, England), 40, 70. doi:10.1007/s12032-022-01926-2. https://pubmed.ncbi.nlm.nih.gov/36588128/
3. Zhou, Hailang, Zou, Junwei, Han, Jingli, Zhou, Aijun, Huang, Shu. 2024. P4HA3 promotes colon cancer cell escape from macrophage phagocytosis by increasing phagocytosis immune checkpoint CD47 expression. In Molecular and cellular biochemistry, 479, 3355-3374. doi:10.1007/s11010-024-04927-z. https://pubmed.ncbi.nlm.nih.gov/38347264/
4. Yu, Chunlai, You, Mingliang, Zhang, Peizhen, Yin, Yuzhu, Zhang, Xiao. 2021. A five-gene signature is a prognostic biomarker in pan-cancer and related with immunologically associated extracellular matrix. In Cancer medicine, 10, 4629-4643. doi:10.1002/cam4.3986. https://pubmed.ncbi.nlm.nih.gov/34121340/
5. Xiao, Zezhou, Reddy, Desai Pavan Kumar, Xue, Chuqing, Ling, Xiao, Zheng, Shaoyi. 2021. Profiling of miR-205/P4HA3 Following Angiotensin II-Induced Atrial Fibrosis: Implications for Atrial Fibrillation. In Frontiers in cardiovascular medicine, 8, 609300. doi:10.3389/fcvm.2021.609300. https://pubmed.ncbi.nlm.nih.gov/33981730/
6. Shi, Run, Gao, Shanshan, Zhang, Jie, Yang, Xiaowen, Li, Chaoyang. . Collagen prolyl 4-hydroxylases modify tumor progression. In Acta biochimica et biophysica Sinica, 53, 805-814. doi:10.1093/abbs/gmab065. https://pubmed.ncbi.nlm.nih.gov/34009234/
7. Wang, Quannian, Meng, Danyang, Shen, Si, Shao, Changli, Dong, Qingyang. 2024. P4HA3 promotes head and neck squamous cell carcinoma progression via the WNT/β-catenin signaling pathway. In Pathology, research and practice, 260, 155481. doi:10.1016/j.prp.2024.155481. https://pubmed.ncbi.nlm.nih.gov/39053135/
8. Zhou, Hailang, Zou, Junwei, Shao, Changjiang, Chen, Song, Xu, Chunfang. 2021. Prolyl 4-hydroxylase subunit alpha 3 facilitates human colon cancer growth and metastasis through the TGF-β/Smad signaling pathway. In Pathology, research and practice, 230, 153749. doi:10.1016/j.prp.2021.153749. https://pubmed.ncbi.nlm.nih.gov/34959098/
9. Wu, Yinteng, Zhang, Bo, Nong, Juan, Zhao, Shijian, Wei, Ruqiong. 2023. Systematic pan-cancer analysis of the potential tumor diagnosis and prognosis biomarker P4HA3. In Frontiers in genetics, 14, 1045061. doi:10.3389/fgene.2023.1045061. https://pubmed.ncbi.nlm.nih.gov/37035741/
10. Niu, Xiaoji, Ren, Liman, Wang, Shoumei, Qi, Hongjun, Zhang, Shuhui. 2022. High Prolyl 4-Hydroxylase Subunit Alpha 3 Expression as an Independent Prognostic Biomarker and Correlated With Immune Infiltration in Gastric Cancer. In Frontiers in genetics, 13, 952335. doi:10.3389/fgene.2022.952335. https://pubmed.ncbi.nlm.nih.gov/35846138/