PDF(Pubmed)
Abstract：
UNASSIGNED: The members retinoic acid receptors (RARs) (α, β, and γ) and retinoid X receptors (RXRs) (α, β, and γ) belong to the retinoid receptor family. They regulate the biological action of classical retinoids through nuclear retinoid receptors, a transcription factor that is regulated by ligands. Through the binding of particular retinoic acid-responsive elements (RAREs) located in target gene promoters, RARs and members of the RXRs form heterodimers. By binding to its nuclear receptors and triggering the transcription of the target genes downstream, retinoic acid (RA) mediates the expression of certain genes. Retinoids so mainly control gene expression to carry out their biological actions. RARs are essential for many biological processes, such as development, immunity, reproduction, organogenesis, and homeostasis. Apart from their physiological functions, RARs are also linked to pathologies and tumors due to mutations, protein fusions, changes in expression levels, or abnormal post-translational changes that lead to aberrant functions and homeostasis breakdown. The oncogenic development of animal tissues or cultured cells is linked to altered expression of retinoid receptors. The RAR-α is over-expressed in several malignancies. Increased invasion and migration in several cancer forms, including HNSC carcinoma, pediatric low-grade gliomas, lung adenocarcinoma, and breast cancer, have been linked to its upregulated expression. Numerous approved therapeutic regimens targeting RAR-α have been developed, improving patient survival rates.
UNASSIGNED: This study\'s main objective was to identify novel RAR-α-targeting drugs and evaluate the expression patterns of RAR-α in breast cancer patients.
UNASSIGNED: In-silico investigation using a variety of bioinformatics tools like UALCAN, TISCH, TIMER 2.0, ENRICHR, and others were employed to examine the expression of RAR-α. Further we evaluated in-silico inhibition of RAR-α with trifarotene and also tested the cytotoxicity of trifarotene in breast cancer cells.
UNASSIGNED: Our research indicates that RAR-α is upregulated in several malignancies including Breast Cancer. It regulates granulocyte differentiation and has an association with the retinoic acid receptor signaling pathway and cellular response to estrogen stimulus. Furthermore, trifarotene was found as a potential synthetic compound that targets RAR-α through in silico and in-vitro study.
UNASSIGNED: Overall, this research indicates that elevated expression of RAR-α enhances the onset of breast cancer. Using trifarotene medication to target RAR-α will significantly boost the response of breast cancer individuals to treatment and delay the development of resistance to drugs.
UNASSIGNED: This study\'s main objective was to identify novel RAR-α-targeting drugs and evaluate the expression patterns of RAR-α in breast cancer patients.
UNASSIGNED: In-silico investigation using a variety of bioinformatics tools like UALCAN, TISCH, TIMER 2.0, ENRICHR, and others were employed to examine the expression of RAR-α. Further we evaluated in-silico inhibition of RAR-α with trifarotene and also tested the cytotoxicity of trifarotene in breast cancer cells.
UNASSIGNED: Our research indicates that RAR-α is upregulated in several malignancies including Breast Cancer. It regulates granulocyte differentiation and has an association with the retinoic acid receptor signaling pathway and cellular response to estrogen stimulus. Furthermore, trifarotene was found as a potential synthetic compound that targets RAR-α through in silico and in-vitro study.
UNASSIGNED: Overall, this research indicates that elevated expression of RAR-α enhances the onset of breast cancer. Using trifarotene medication to target RAR-α will significantly boost the response of breast cancer individuals to treatment and delay the development of resistance to drugs.
摘要：
■成员视黄酸受体（RAR）（α，β,和γ）和类维生素AX受体（RXRs）（α，β,和γ）属于类维生素A受体家族。它们通过核类维生素A受体调节经典类维生素A的生物学作用，由配体调节的转录因子。通过位于靶基因启动子中的特定视黄酸响应元件（RARE）的结合，RAR和RXR的成员形成异二聚体。通过与其核受体结合并触发下游靶基因的转录，维甲酸（RA）介导某些基因的表达。因此类维生素A主要控制基因表达以实现其生物学作用。RAR对许多生物过程至关重要，如发展,豁免权,繁殖，器官发生，和稳态。除了他们的生理功能，由于突变，RAR也与病理和肿瘤有关，蛋白质融合，表达水平的变化，或导致功能异常和稳态破坏的异常翻译后变化。动物组织或培养细胞的致癌发育与类视黄醇受体的表达改变有关。RAR-α在几种恶性肿瘤中过度表达。几种癌症形式的侵袭和迁移增加，包括HNSC癌,小儿低度胶质瘤，肺腺癌,和乳腺癌，已经与其上调的表达有关。已经开发了许多批准的靶向RAR-α的治疗方案，提高患者生存率。
■本研究的主要目的是鉴定新型RAR-α靶向药物并评估RAR-α在乳腺癌患者中的表达模式。
■使用UALCAN等多种生物信息学工具进行计算机内调查，TISCH,TIMER2.0,ENRICHR,和其他人被用来检查RAR-α的表达。进一步，我们评估了三法罗汀对RAR-α的计算机内抑制作用，并测试了三法罗汀在乳腺癌细胞中的细胞毒性。
■我们的研究表明RAR-α在包括乳腺癌在内的多种恶性肿瘤中上调。它调节粒细胞分化，并与视黄酸受体信号通路和细胞对雌激素刺激的反应有关。此外，通过计算机和体外研究，发现trifarotene是一种潜在的针对RAR-α的合成化合物。
■总的来说，这项研究表明RAR-α的高表达增强了乳腺癌的发病。使用trifarotene药物靶向RAR-α将显着增强乳腺癌个体对治疗的反应并延迟对药物的耐药性发展。
■本研究的主要目的是鉴定新型RAR-α靶向药物并评估RAR-α在乳腺癌患者中的表达模式。
■使用UALCAN等多种生物信息学工具进行计算机内调查，TISCH,TIMER2.0,ENRICHR,和其他人被用来检查RAR-α的表达。进一步，我们评估了三法罗汀对RAR-α的计算机内抑制作用，并测试了三法罗汀在乳腺癌细胞中的细胞毒性。
■我们的研究表明RAR-α在包括乳腺癌在内的多种恶性肿瘤中上调。它调节粒细胞分化，并与视黄酸受体信号通路和细胞对雌激素刺激的反应有关。此外，通过计算机和体外研究，发现trifarotene是一种潜在的针对RAR-α的合成化合物。
■总的来说，这项研究表明RAR-α的高表达增强了乳腺癌的发病。使用trifarotene药物靶向RAR-α将显着增强乳腺癌个体对治疗的反应并延迟对药物的耐药性发展。
