Overexpression of TRIM28 predicts an unfavorable prognosis and promotes the proliferation and migration of hepatocellular carcinoma
Overexpression of TRIM28 predicts an unfavorable prognosis and promotes the proliferation and migration of hepatocellular carcinoma
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DOI：
10.1515/oncologie-2023-0118
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发表时间：
2023-07
期刊：
影响因子：
0.9
通讯作者：
Yu-ji Chen;Jinshu Pang;Weirong Liao;Wei Wan;Tong Kang;Xiang-Yu Gan;P. Lin;Dong-Yue Wen;Yun He;Hong-tao Yang
中科院分区：
文献类型：
--
作者：
Yu-ji Chen;Jinshu Pang;Weirong Liao;Wei Wan;Tong Kang;Xiang-Yu Gan;P. Lin;Dong-Yue Wen;Yun He;Hong-tao Yang
摘要目的TRIM 28可能是肿瘤治疗的潜在靶点。然而，TRIM 28在肝细胞癌（HCC）中的详细作用和机制仍不明确。方法我们基于大规模数据和公开可用的免疫组化图像，系统地分析了HCC组织中TRIM 28 mRNA表达和蛋白水平。我们估计了TRIM 28在HCC中的预后能力。此外，我们进行了基因富集、免疫浸润和药物敏感性分析，以进一步探索TRIM 28在HCC中的作用。为了确定TRIM 28表达对HCC细胞增殖和迁移的影响，在MHCC 97-L和Huh 7细胞中进行siRNA的成功转染，随后进行细胞功能测定。结果在mRNA和蛋白水平证实了TRIM 28在HCC中的高表达。曲线下面积为0.84（95%CI：0.81-0.87）的概括受试者工作特征曲线表明增加TRIM 28表达用于区分HCC与非HCC组织的高准确性。根据癌症基因组图谱数据集，TRIM 28 mRNA表达与年龄、分级、分期和病理T显著相关（p<0.05）。TRIM 28表达水平的增加与HCC患者的不良生存率显著相关。富集分析表明，TRIM 28相关基因主要参与剪接体信号传导途径，中枢基因包括SNRPA 1、SNRPF、SNRPD 1、SF 3B 2、SNRPB、SNRPE和EFTUD 2。TRIM 28的表达与5种免疫细胞的浸润相关。较高的TRIM 28表达与肿瘤细胞对pluripotin的更好敏感性有关。分子对接表明，pluripotin可以结合TRIM 28。此外，TRIM 28的敲低抑制HCC细胞的增殖和迁移。结论TRIM 28在肝癌组织中高表达，促进肝癌细胞的增殖和迁移，导致不良预后。这些发现表明TRIM 28有望成为一种新的预后指标。
Abstract Objectives Previous studies have shown that tripartite motif-containing 28 (TRIM28) might be a latent target for cancer therapy. However, the detailed roles and mechanisms of TRIM28 in hepatocellular carcinoma (HCC) remain ambiguous. Methods We systematically analyzed TRIM28 mRNA expression and protein levels in HCC tissues based on large-scale data and publicly available immunohistochemistry images. We estimated the prognostic capacity of TRIM28 in HCC. Additionally, we performed gene enrichment, immune infiltration, and drug sensitivity analyses to further explore the roles of TRIM28 in HCC. To determine the effect of TRIM28 expression on HCC cell proliferation and migration, successful transfection of siRNAs was conducted in MHCC97-L and Huh7 cells, followed by cell functional assays. Results We verified the overexpression of TRIM28 in HCC at the mRNA and protein levels. The summary receiver operating characteristics curve with the area under curve of 0.84 (95 % CI: 0.81–0.87) indicated the high accuracy of increasing TRIM28 expression for discriminating HCC from non-HCC tissues. According to The Cancer Genome Atlas datasets, TRIM28 mRNA expression was significantly related to age, grade, stage, and pathologic T (p<0.05). Increased TRIM28 expression levels were significant correlated to poor survival in HCC patients. An enrichment analysis suggested that TRIM28-reated genes primarily participated in the spliceosome signaling pathway, with hub genes including SNRPA1, SNRPF, SNRPD1, SF3B2, SNRPB, SNRPE, and EFTUD2. TRIM28 expression was correlated with the infiltration of five immune cells. Higher TRIM28 expression was linked to better sensitivity of tumor cells to pluripotin. Molecular docking showed that pluripotin could bind to TRIM28. Further, knockdown of TRIM28 inhibited the proliferation and migration of HCC cells. Conclusions TRIM28 is highly expressed in HCC and contribute to the proliferation and migration of HCC cells, leading to unfavorable outcomes. These findings indicate TRIM28 promise as a novel prognostic indicator.