组氨酸三联体核苷酸结合蛋白1在人类癌症中的致癌和免疫作用及其在MCF-7细胞系中的实验验证。
The oncogenic and immunological roles of histidine triad nucleotide-binding protein 1 in human cancers and their experimental validation in the MCF-7 cell line.
作者信息
Wang Xuzhen, Zhou Min, Jiang Liping
机构信息
Department of Breast Surgery, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, China.
Department of Gynecology, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, China.
出版信息
Ann Transl Med. 2023 Feb 15;11(3):147. doi: 10.21037/atm-22-6637.
BACKGROUND
Histidine triad nucleotide binding protein 1 () is a haplo-insufficient tumor suppressor gene that plays a significant role in cell proliferation and survival. However, to date, no systematic pan-cancer analysis has been conducted to explore its function in prognosis, and its oncogenic and immunological roles. We also analyzed the role of in breast cancer (BC) progression .
METHODS
An analysis of the expression pattern was performed using the TIMER database. The infiltration of immune cells into several cancer types was also studied using the Xena Shiny tool. To determine the relationship between stemness and the expression of mRNA, the Spearman correlation test was used with the SangerBox tool. The correlation between and functional states in various cancers was determined from the CancerSEA database. The potential role of in BC oncogenesis was also investigated by Western blot and Annexin V/PI assays.
RESULTS
The Cancer Genome Atlas pan-cancer data analysis suggested that was extensively altered in most tumor tissues but not in most adjacent normal tissues. A high expression of was associated with the decreased infiltration of cluster of differentiation (CD)4 T cells. Importantly, increased expression was also associated with a large majority of tumors with high stemness and lower stromal, immune, and estimate scores. Further, the expression of was significantly associated with the tumor mutational burden (TMB) and microsatellite instability (MSI) in certain tumor types. Finally, overexpression was found to impair BC progression by promoting cell apoptosis. upregulation also reduced the expression of microphthalmia transcription factor () and β-catenin in BC Michigan Cancer Foundation-7 (MCF-7) cells, and the phosphorylation of protein kinase B (p-Akt).
CONCLUSIONS
The present study showed that plays an oncogenic role in various cancers and could also be used as a biomarker for BC.
背景
组氨酸三联体核苷酸结合蛋白1（HINT1）是一种单倍体不足的肿瘤抑制基因，在细胞增殖和存活中起重要作用。然而，迄今为止，尚未进行系统的泛癌分析来探讨其在预后、致癌和免疫作用方面的功能。我们还分析了HINT1在乳腺癌（BC）进展中的作用。
方法
使用TIMER数据库对HINT1表达模式进行分析。还使用Xena Shiny工具研究免疫细胞向几种癌症类型的浸润情况。为了确定干性与HINT1 mRNA表达之间的关系，使用SangerBox工具进行Spearman相关性检验。从CancerSEA数据库确定HINT1与各种癌症功能状态之间的相关性。还通过蛋白质印迹和膜联蛋白V/PI分析研究了HINT1在BC肿瘤发生中的潜在作用。
结果
癌症基因组图谱泛癌数据分析表明，HINT1在大多数肿瘤组织中广泛改变，但在大多数相邻正常组织中未改变。HINT1高表达与分化簇（CD）4 T细胞浸润减少有关。重要的是，HINT1表达增加也与大多数具有高干性以及较低基质、免疫和估计评分的肿瘤有关。此外，在某些肿瘤类型中，HINT1的表达与肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）显著相关。最后，发现HINT1过表达通过促进细胞凋亡来损害BC进展。HINT1上调还降低了BC密歇根癌症基金会-7（MCF-7）细胞中小眼畸形转录因子（MITF）和β-连环蛋白的表达，以及蛋白激酶B（p-Akt）的磷酸化。
结论
本研究表明，HINT1在各种癌症中起致癌作用，也可作为BC的生物标志物。
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