CT23 knockdown attenuating malignant behaviors of hepatocellular carcinoma cell is associated with upregulation of metallothionein 1.
CT23 knockdown attenuating malignant behaviors of hepatocellular carcinoma cell is associated with upregulation of metallothionein 1.
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CT23 敲低减轻肝细胞癌细胞的恶性行为与金属硫蛋白 1 的上调相关。
DOI：
10.1002/cbin.11567
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发表时间：
2021
影响因子：
3.9
通讯作者：
Hu Qiping
中科院分区：
文献类型：
--
作者：
Ning Wanjing;Huang Miao;Wu Shengming;Wang Hong;Yao Jiali;Ge Yingying;Tang Yulu;Sun Kejian;Xie Xiaoxun;Hu Qiping
据报道，癌睾丸抗原23 （CT23）基因与肝细胞癌（HCC）的发病和进展有关。然而，CT23敲低在HCC细胞中引起的基因表达谱改变在很大程度上仍然未知。在本研究中，采用RNA干扰（RNAi）方法沉默BEL‐7404细胞中CT23的表达。对CT23敲除细胞和对照细胞中提取的mRNA进行微阵列分析，以确定基因表达谱的变化。结果显示，共有1051个基因表达差异（2倍变化），其中CT23敲低细胞中有470个基因表达上调，581个基因表达下调。生物信息学分析表明，功能差异表达基因（DEGs）与细胞增殖、迁移和凋亡有关，金属硫蛋白1 （metallothionein 1, MT1）在DEGs的功能注释、分类和通路分析中获得了最高的富集分数。此外，Western blot分析和细胞行为分析证实，CT23通过调节MT1在HCC细胞和非肿瘤性肝细胞中的表达来调节细胞增殖、迁移和凋亡。综上所述，BEL‐7404细胞中CT23基因的下调可能通过上调MT1的表达而改变HCC中癌发生和进展相关基因的表达，这将为寻找新的HCC治疗靶点提供新的见解。
The cancer‐testis antigen 23 (CT23) gene has been reported in association with the pathogenesis and progress of hepatocellular carcinoma (HCC). However, the alterations of gene expression profiling induced by CT23 knockdown in HCC cells remains largely unknown. In this study, the RNA interfering (RNAi) method was used to silence CT23 expression in BEL‐7404 cells. Microarray analysis was performed on mRNA extracted from the CT23 knockdown cells and the control cells to determine the alterations of gene expression profiles. The result showed a total of 1051 genes expressed differentially (two‐fold change), including 470 genes upregulated and 581 gene downregulated in the CT23 knockdown cells. A bioinformatic analysis showed that the functional differentially expressed genes (DEGs) were linked to cell proliferation, migration, and apoptosis, and metallothionein 1 (MT1) attained the maximum enrichment scores in functional annotation, classification, and pathway analysis of DEGs. Furthermore, Western blot analysis and cell behaviors assays verified that CT23 modulates cell proliferation, migration, and apoptosis by regulating MT1 expression in HCC cells and non‐neoplastic hepatocytes. In summary, downregulated CT23 gene in BEL‐7404 cells might change the expressions of carcinogenesis and progression related genes in HCC by upregulating MT1 expression, which would provide insight into searching for a novel therapeutic target for HCC.