更新于：2024-09-19

OVOL2

更新于：2024-09-19

基本信息

别名

bA504H3.3、CHED、CHED1

+ [6]

简介

Zinc-finger transcription repressor factor (PubMed:19700410). Plays a critical role in maintaining the identity of epithelial lineages by suppressing epithelial-to mesenchymal transition (EMT) mainly through the repression of ZEB1, an EMT inducer (By similarity). Positively regulates neuronal differentiation (By similarity). Suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing MYC and NOTCH1 (PubMed:19700410). Important for the correct development of primordial germ cells in embryos (By similarity). Plays dual functions in thermogenesis and adipogenesis to maintain energy balance. Essential for brown/beige adipose tissue-mediated thermogenesis, is necessary for the development of brown adipocytes. In white adipose tissues, limits adipogenesis by blocking CEBPA binding to its transcriptional targets and inhibiting its transcription factor activity (By similarity).

关联

100 项与 OVOL2 相关的临床结果

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100 项与 OVOL2 相关的转化医学

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0 项与 OVOL2 相关的专利（医药）

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105

项与 OVOL2 相关的文献（医药）

2024-07-04·Microscopy and Microanalysis

Expression Patterns of Grainyhead-Like 2 and Ovo-Like 2 in Mouse Mammary Gland Development During Pregnancy, Lactation, and Weaning

Article

作者: Matsuoka, Shinya ; Nakamura, Kazuki ; Elfeky, Mohamed ; Suzuki, Hiroyoshi ; Kamikawa, Akihiro ; Elewa, Yaser Hosny Ali ; Yamamoto, Izumi ; Kimura, Kazuhiro ; Okamatu-Ogura, Yuko

AbstractGrainyhead-like 2 (Grhl2) is a transcription factor that regulates cell adhesion genes in mammary ductal development and serves as a repressor of the epithelial–mesenchymal transition. Conversely, Ovo-like2 (Ovol2) is a target gene of Grhl2 but functions as a substitute in Grhl2-deficient mice, facilitating successful epithelial barrier formation and lumen expansion in kidney-collecting ductal epithelial cells. Our objective was to examine the expression patterns of Grhl2, Ovol2, and their associated genes during the intricate phases of mouse mammary gland development. The mRNA expression of Grhl2 and Ovol2 increased after pregnancy. We observed Grhl2 protein presence in the epithelial cell's region, coinciding with acini formation, and its signal significantly correlated with E-cadherin (Cdh1) expression. However, Ovol2 was present in the epithelial region without a correlation with Cdh1. Similarly, Zeb1, a mesenchymal transcription factor, showed Cdh1-independent expression. Subsequently, we explored the interaction between Rab25, a small G protein, and Grhl2/Ovol2. The expressions of Grhl2 and Ovol2 exhibited a strong correlation with Rab25 and claudin-4, a tight junction protein. These findings suggest that Grhl2 and Ovol2 may collaborate to regulate genes associated with cell adhesion and are crucial for maintaining epithelial integrity during the different phases of mammary gland development.

2024-06-01·Advanced Science

Loss of OVOL2 in Triple‐Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics

Article

作者: Lu, Ruipeng ; Li, Boan ; Zhu, Yu ; Fu, Tong ; Zhang, Rui ; Tong, Ruiqi ; Hong, Jingjing ; Wang, Shuai ; Zhang, Zhiming ; Chen, Ceshi ; Guo, Huiling ; Ai, Di ; Huang, Qingsong

AbstractTriple‐negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo‐like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere‐forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT‐Ovol2 knockout mice develop a higher number of primary breast tumors with accelerated growth and increased lung‐metastases. Furthermore, treatment with FAO inhibitors effectively reduces stemness characteristics of tumor cells, breast tumor initiation, and metastasis, especially in OVOL2‐deficient breast tumors. The findings suggest that targeting JAK/STAT3 pathway and FAO is a promising therapeutic strategy for OVOL2‐deficient TNBC.

2024-02-28·Human Molecular Genetics

Ovol2 promoter mutations in mice and human illuminate species-specific phenotypic divergence

Article

作者: Lachova, Jitka ; Sunny, Sweetu Susan ; Palkova, Marcela ; Kozmik, Zbynek ; Liskova, Petra ; Kasparek, Petr ; Prochazka, Jan ; Spoutil, Frantisek ; Sedlacek, Radislav

AbstractPathogenic variants in the highly conserved OVOL2 promoter region cause posterior polymorphous corneal dystrophy (PPCD) 1 by inducing an ectopic expression of the endothelial OVOL2 mRNA. Here we produced an allelic series of Ovol2 promoter mutations in the mouse model including the heterozygous c.-307T>C variant (RefSeq NM_021220.4) causing PPCD1 in humans. Despite the high evolutionary conservation of the Ovol2 promoter, only some alterations of its sequence had phenotypic consequences in mice. Four independent sequence variants in the distal part of the Ovol2 promoter had no significant effect on endothelial Ovol2 mRNA level or caused any ocular phenotype. In contrast, the mutation c.-307T>C resulted in increased Ovol2 expression in the corneal endothelium. However, only a small fraction of adult mice c.-307T>C heterozygotes developed ocular phenotypes such as irido-corneal adhesions, and corneal opacity. Interestingly, phenotypic penetrance was increased at embryonic stages. Notably, c.-307T>C mutation is located next to the Ovol1/Ovol2 transcription factor binding site. Mice carrying an allele with a deletion encompassing the Ovol2 binding site c.-307_-320del showed significant Ovol2 gene upregulation in the cornea endothelium and exhibited phenotypes similar to the c.-307T>C mutation. In conclusion, although the mutations c.-307T>C and -307_-320del lead to a comparably strong increase in endothelial Ovol2 expression as seen in PPCD1 patients, endothelial dystrophy was not observed in the mouse model, implicating species-specific differences in endothelial cell biology. Nonetheless, the emergence of dominant ocular phenotypes associated with Ovol2 promoter variants in mice implies a potential role of this gene in eye development and disease.

项与 OVOL2 相关的新闻（医药）

2024-05-01

·今日头条

攻坚克难！厦门大学李博安/郭慧玲等合作发现“最毒乳腺癌”治疗新策略

本文为转化医学网原创，转载请注明出处作者：Jerry 导读：三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，预后差且缺乏有效的治疗策略，被称为“最毒乳腺癌”。近日，厦门大学李博安、郭慧玲及昆明医科大学Zhang Rui共同通讯在Advanced Science 在线发表题为“Loss of OVOL2 in Triple-Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics”的研究论文，该研究发现TNBC中转录因子OVOL2的表达降低。OVOL2的缺失促进脂肪酸氧化（FAO），提供更多能量和NADPH维持细胞干性特征，包括肿瘤组织形成能力和肿瘤增殖。研究结果表明，靶向JAK/STAT3通路和FAO是治疗OVOL2缺陷型TNBC的一种有效策略。 https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/10.1002/advs.202308945 研究背景 01 三阴性乳腺癌（TNBC）缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2），是最具侵袭性的亚型，占所有乳腺癌病例的10-20%。TNBC的高干性特征促进癌症快速生长和远端转移。由于缺乏ER、PR和HER2受体，传统的激素靶向疗法和HER2靶向疗法对三阴性乳腺癌的治疗效果较差。化疗虽然是主要选择方式，但效果有限。因此，开发新的TNBC治疗策略至关重要。脂肪酸β-氧化（FAO）在癌细胞代谢中起着至关重要的作用，提供维持细胞快速生长和肿瘤进展所必需的大量能量。此外，FAO大量产生NADPH等抗氧化剂，可促进肿瘤细胞的存活。FAO在癌症进展、化疗耐药性和维持癌症干细胞（CSCs）方面的作用引起了广泛关注，抑制FAO是一种治疗乳腺癌的潜在方法。然而，仍不清楚FAO在三阴性乳腺癌中的具体作用机制。研究进展 02 在实验中ETO治疗可以减少肿瘤细胞的球形形成，所以研究人员推断抑制FAO可能是预防肿瘤发生的理想策略。临床上用于抗心绞痛治疗的CPT1抑制剂哌克昔林被用于给PyVT-Ovol2WT和PyVT-Ovol2KO小鼠注射，在肿瘤可触及后连续治疗21天。与WT小鼠相比，哌克昔林治疗显著改善了OVOL2缺陷小鼠的总体生存情况。此外，哌克昔林通过灌胃在体内抑制FAO，减少了Ovol2KO肿瘤细胞的球形形成。缺乏OVOL2的肿瘤细胞具有更高的肿瘤发生能力，这种能力被哌克昔林治疗有效抑制。本研究结果表明，OVOL2缺失通过调节FAO促进MMTV-PyVT小鼠的肿瘤发生，从而表明FAO抑制剂在乳腺癌治疗中的潜在临床价值。此外，研究人员还观察了哌克昔林对小鼠原发性乳腺肿瘤生长的影响。在哌克昔林治疗后，PyVT-Ovol2KO肿瘤的生长显著低于PBS处理组。对转移灶的成像和定量分析显示，在哌克昔林治疗后，PyVT-Ovol2KO小鼠的肺转移显著减少。免疫组化染色显示，哌克昔林抑制了OVOL2缺失肿瘤中观察到的细胞增殖和转化，其程度与对照组肿瘤相比有所降低。同样，在体内，研究人员旨在验证JAK/STAT通路是OVOL2的关键下游靶点。JAK1抑制剂乌帕替尼(Upa)的使用大大减弱了由OVOL2缺乏诱导的致瘤性促进。这些发现清楚地表明，在OVOL2缺乏的小鼠中，FAO和JAK/STAT3通路对乳腺肿瘤进展的要求。此外，这些结果提供了令人信服的证据，证明OVOL2的缺失激活了JAK/STAT3通路并增强了FAO，从而使肿瘤对哌克昔林或乌帕替尼治疗更敏感。这表明，靶向FAO或JAK/STAT途径是治疗ovol2缺陷TNBC的一种有希望的治疗策略。靶向JAK或FAO来抑制OVOL2敲除小鼠的乳腺肿瘤进展研究结论 03 总之，本研究揭示了OVOL2作为一种肿瘤抑制因子在乳腺癌中的新机制，通过STAT3信号通路和FAO抑制来抑制肿瘤干性及转移。调节这些分子过程可能为癌症治疗提供新的靶向治疗策略。参考资料： https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/10.1002/advs.202308945 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 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！点击对应文字查看详情

临床研究临床结果