Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar 190006, India.
Department of Biotechnology, School of Biological Sciences, University of Kashmir, Srinagar 190006, India.
Comput Biol Chem. 2024 Oct;112:108164. doi: 10.1016/j.compbiolchem.2024.108164. Epub 2024 Jul 26.
Breast carcinoma is the leading factor in women's cancer-related fatalities. Due to its numerous inherent molecular subtypes, breast cancer is an extremely diverse illness. The human epidermal growth factor receptor 2 (HER2) positive subtypes stands out among these subtypes as being especially prone to cancer development and illness recurrence. The regulation of embryonic stem cells' pluripotency and self-renewal is carried out by the SALL4 (Spalt-like transcription factor 4) family member. Numerous molecular pathways operating at the transcriptional, post-transcriptional, and epigenomic levels regulate the expression of SALL4. Many transcription factors control the expression of SALL4, with STAT3 being the primary regulator in hepatocellular carcinoma (HCC) and breast carcinoma. Moreover, this oncogene has been connected to a number of cellular functions, including invasion, apoptosis, proliferation, and resistance to therapy. Reduced patient survival rates and a worse prognosis have been linked to higher levels of SALL4. In order to target the undruggable SALL4 that is overexpressed in breast carcinoma, we investigated the prognostic levels of SALL4 in breast carcinoma and its interaction with various related proteins. Using TIMER 2.0 analysis, the expression pattern of SALL4 was investigated across all TCGA datasets. The research revealed that SALL4 expression was elevated in various cancers. The UALCAN findings demonstrated that SALL4 was overexpressed in all tumor samples including breast cancer especially TNBC (Triple negative breast cancer). The web-based ENRICHR program was used for gene ontology analysis that revealed SALL4 was actively involved in the development of the nervous system, positive regulation of stem cell proliferation, regulation of stem cell proliferation, regulation of the activin receptor signaling pathway, regulation of transcription using DNA templates, miRNA metabolic processes, and regulation of transcription by RNA Polymerase I. Using the STRING database, we analyzed the interaction and involvement of SALL4 with other abruptly activated proteins and used Cytoscape 3.8.0 for visualization. Additionally, using bc-GenExMiner, we studied the impact of SALL4 on pathways abruptly activated in different breast cancer subtypes that revealed SALL4 was highly correlated with WNT2B, NOTCH4, AKT3, and PIK3CA. Furthermore, to target SALL4, we evaluated and analyzed the impact of CLP and its analogues, revealing promising outcomes.
乳腺癌是导致女性癌症相关死亡的主要因素。由于其众多内在的分子亚型，乳腺癌是一种极其多样化的疾病。在这些亚型中，人表皮生长因子受体 2（HER2）阳性亚型尤其容易发生癌症发展和疾病复发。SALL4（Spalt-like 转录因子 4）家族成员调节胚胎干细胞的多能性和自我更新。许多分子途径在转录、转录后和表观遗传水平上调节 SALL4 的表达。许多转录因子控制 SALL4 的表达，其中 STAT3 是肝癌（HCC）和乳腺癌的主要调节因子。此外，这个癌基因与许多细胞功能有关，包括侵袭、凋亡、增殖和对治疗的耐药性。SALL4 水平升高与患者生存率降低和预后不良有关。为了靶向在乳腺癌中过度表达的不可成药的 SALL4，我们研究了 SALL4 在乳腺癌中的预后水平及其与各种相关蛋白的相互作用。使用 TIMER 2.0 分析，在所有 TCGA 数据集上研究了 SALL4 的表达模式。研究表明，SALL4 在各种癌症中表达升高。UALCAN 的研究结果表明，SALL4 在所有肿瘤样本中均过表达，包括乳腺癌，尤其是三阴性乳腺癌（TNBC）。使用基于网络的 ENRICHR 程序进行基因本体分析表明，SALL4 积极参与神经系统的发育、干细胞增殖的正调控、干细胞增殖的调控、激活素受体信号通路的调控、使用 DNA 模板的转录调控、miRNA 代谢过程和 RNA 聚合酶 I 介导的转录调控。使用 STRING 数据库，我们分析了 SALL4 与其他突然激活的蛋白质的相互作用和参与，并使用 Cytoscape 3.8.0 进行可视化。此外，使用 bc-GenExMiner，我们研究了 SALL4 对不同乳腺癌亚型中突然激活的途径的影响，结果表明 SALL4 与 WNT2B、NOTCH4、AKT3 和 PIK3CA 高度相关。此外，为了靶向 SALL4，我们评估和分析了 CLP 及其类似物的影响，结果显示出有希望的结果。
