UTP11 通过增强 Oct4 的 mRNA 稳定性促进肝癌的生长。
UTP11 promotes the growth of hepatocellular carcinoma by enhancing the mRNA stability of Oct4.
机构信息
Department of Gastroenterology, The Second Affiliated Hospital of Shandong First Medical University, Tai an City, China.
Department of Endoscopy Center, The Second Affiliated Hospital of Shandong First Medical University, Tai an City, China.
出版信息
BMC Cancer. 2024 Jan 17;24(1):93. doi: 10.1186/s12885-023-11794-2.
BACKGROUND
Several publications suggest that UTP11 may be a promising gene engaged for involvement of hepatocellular carcinoma (HCC) pathology. However, there are extremely limited biological, mechanistic and clinical studies of UTP11 in HCC.
METHODS
To anayze the UTP11 mRNA expression in HCC and normal clinical samples and further investigate the correlation between UTP11 expression and pathology and clinical prognosis via the Cancer Tissue Gene Atlas (TCGA) database. The protein levels of UTP11 were checked using the Human Protein Atlas (HPA) database. GO-KEGG enrichment was performed from Cancer Cell Line Encyclopedia (CCLE) database and TCGA dataset. The levels of UTP11 were tested with qRT-PCR and western blotting assays. Cell viability, immunofluorescence and flow cytometry assays and animal models were used to explore the potential involvement of UTP11 in regulating HCC growth in vitro and in vivo. The correlation of UTP11 and tumor stemness scores and stemness-associated proteins from TCGA database. The mRNA stability was treated with Actinomycin D, followed by testing the mRNA expression using qRT-PCR assay.
RESULTS
UTP11 was highly expressed in HCC samples compared to normal tissues from TCGA database. Similarly, UTP11 protein expression levels were obviously elevated in HCC tissue samples from HPA database. Furthermore, UTP11 levels were correlated with poor prognosis in HCC patient samples in TCGA dataset. In addition, the UTP11 mRNA levels was notably enhanced in different HCC cell lines than in normal liver cells and knocking down UTP11 was obviously reduced the viability and cell death of HCC cells. UTP11 knockdown suppressed the tumor growth of HCC in vivo experiment and extended the mice survival time. GO-KEEG analysis from CCLE and TCGA database suggested that UTP11 might involve in RNA splicing and the stability of mRNA. Further, UTP11 was positively correlated with tumor stemness scores and stemness-associated proteins from TCGA database. Knockdown of UTP11 was reduced the expression of stem cell-related genes and regulated the mRNA stability of Oct4.
CONCLUSIONS
UTP11 is potentially a diagnostic molecule and a therapeutic candidate for treatment of HCC.
背景
有几项研究表明，UTP11 可能是参与肝细胞癌（HCC）发病机制的一个很有前途的基因。然而，目前关于 HCC 中 UTP11 的生物学、机制和临床研究极为有限。
方法
分析 HCC 和正常临床样本中的 UTP11mRNA 表达，并进一步通过癌症组织基因图谱（TCGA）数据库研究 UTP11 表达与病理学和临床预后之间的相关性。使用人类蛋白质图谱（HPA）数据库检查 UTP11 的蛋白水平。从癌症细胞系百科全书（CCLE）数据库和 TCGA 数据集进行 GO-KEGG 富集。使用 qRT-PCR 和 Western blot 检测 UTP11 的水平。细胞活力、免疫荧光和流式细胞术检测以及动物模型用于探索 UTP11 在体外和体内调节 HCC 生长中的潜在作用。从 TCGA 数据库中研究 UTP11 与肿瘤干性评分和干性相关蛋白的相关性。用 Actinomycin D 处理 mRNA 稳定性，然后使用 qRT-PCR 检测 mRNA 表达。
结果
TCGA 数据库显示，与正常组织相比，UTP11 在 HCC 样本中高度表达。同样，HPA 数据库中 HCC 组织样本中 UTP11 蛋白表达水平明显升高。此外，TCGA 数据集显示 UTP11 水平与 HCC 患者样本的不良预后相关。此外，与正常肝细胞相比，不同 HCC 细胞系中 UTP11mRNA 水平明显升高，敲低 UTP11 明显降低 HCC 细胞的活力和细胞死亡。UTP11 敲低抑制 HCC 的体内实验肿瘤生长并延长小鼠的生存时间。CCLE 和 TCGA 数据库的 GO-KEEG 分析表明，UTP11 可能参与 RNA 剪接和 mRNA 的稳定性。此外，UTP11 与 TCGA 数据库中的肿瘤干性评分和干性相关蛋白呈正相关。敲低 UTP11 降低了干细胞相关基因的表达，并调节了 Oct4 的 mRNA 稳定性。
结论
UTP11 可能是 HCC 的诊断分子和治疗候选物。
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