Elevation of TRIM44 potentiates propagation of gastric cancer stem cells.
Elevation of TRIM44 potentiates propagation of gastric cancer stem cells.
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DOI：
10.1016/j.gendis.2021.10.008
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发表时间：
2022-09
期刊：
影响因子：
6.8
通讯作者：
Xu, Aman
中科院分区：
文献类型：
--
作者：
Zhu, Hai;Wang, Gang;Sun, Qikai;Zhu, Haixing;Xu, Aman
胃癌干细胞(CSCs)是指治疗难治和自我更新的细胞群，在胃癌的发生、发展过程中起重要作用。1虽然胃CSCs群体已被多项研究证实，2胃CSCs特性维持的确切分子机制仍不清楚。新的证据表明，三方基序(Trim)家族成员通过蛋白质泛素化修饰调控CSCs的自我更新和分化。3然而，TRIM家族成员对GC和胃CSCs的影响尚未阐明。在本研究中，我们发现TRIM家族成员之一的TRIM44在人的胃癌和胃CSCs中高表达，并与胃癌的进展和预后不良有关。此外，我们的研究结果揭示了TRIM44/14-3-3ζ/β-catenin信号在诱导胃肿瘤干细胞特性中的关键作用，从而支持它们作为潜在的治疗靶点来调节GC的增殖和化疗耐药。通过分析公开的GC数据集中TRIM家族成员的表达和预后，我们确定TRIM44是一个潜在的肿瘤促进剂，其表达上调与胃癌的预后不良相关(图4)。S1a、B)。为了进一步确定TRIM44的表达，我们通过免疫组织化学(IHC)染色分析了包含75例GC患者组织的微阵列(图1A，左图)，发现TRIM44在肿瘤组织中的表达显著升高(图1A，右上图)。通过生存分析，我们发现TRIM44与不良预后相关，是总生存期(OS)缩短和无复发生存期(RFS)降低的独立危险因素(图1A，右下图和图1)。S1C-E)。此外，与正常胃细胞系GES1相比，TRIM44在5种胃癌细胞系中的表达均显著升高，尤其是MKN45和AGS细胞系(见图3)。S1F，G)。
Gastric cancer stem cells (CSCs), which refer to treatment-refractory and self-renewal cell populations, are critically involved in the initiation and progression of gastric cancer (GC). 1 Although gastric CSCs populations have been validated across multiple studies, 2 the precise molecular mechanisms of gastric CSCs properties maintenance remain unclear. Emerging evidences have highlighted the role of tripartite-motif (TRIM) family members in regulating CSCs self-renewal and differentiation through protein ubiquitination modification. 3 However, the effects of TRIM family members on GC and gastric CSCs have not been elucidated. In this study, we identified TRIM44 (one of the TRIM family members) is overexpressed in human GC and gastric CSCs, and associates with GC progression and poor prognosis. In addition, our findings revealed a crucial role of TRIM44/14-3-3ζ/β-catenin signaling in inducing gastric CSCs properties, thus supporting their function as potential therapeutic targets in modulating GC proliferation and chemoresistance.By analyzing the expression and prognosis of each TRIM family member in the public GC datasets, we identified TRIM44 as a potential tumor promoter whose expression was upregulated and correlated with poor prognosis in GC (Fig. S1A, B). To further identify TRIM44 expression, we analyzed a microarray containing 75 GC patient tissues by immunohistochemistry (IHC) staining (Fig. 1 A, left panel), and found that TRIM44 expression was significantly elevated in tumor tissues (Fig. 1 A, upper-right panel). Through survival analysis, we found that TRIM44 was correlated with a poor prognosis and was an independent risk factor for shorter overall survival (OS) durations and lower recurrence-free survival (RFS) periods (Fig. 1 A, bottom-right panel, and Fig. S1C–E). Moreover, compared with the normal gastric cell line GES1, the expression of TRIM44 was significantly higher in the five GC cell lines, especially the MKN45 and AGS cell lines (Fig. S1F, G).
影响因子：
9.7
作者：
Tong, Yingying;Guo, Dong;Xing, Dongming
通讯作者：
Xing, Dongming
影响因子：
9.7
作者：
Singh, Shree Ram
通讯作者：
Singh, Shree Ram