High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma.
High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma.
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香橼激酶的高表达有助于食管鳞状细胞癌的发生
DOI：
10.3389/fgene.2021.628547
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发表时间：
2021
影响因子：
3.7
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Lu W;Dong Y;Cui Q;Wang Y;Yang X;Cai X;Zhang M
本研究旨在探讨香橼激酶（CIT）在食管鳞状细胞癌（ESCC）中的作用和潜在调控机制。基于微阵列数据集GSE20347分析ESCC组织中香橼激酶（CIT）的表达，并分析ESCC细胞系中CIT的表达。用shRNA-CIT（LV-shCIT）慢病毒转染Eca-109细胞以敲除CIT，然后研究细胞增殖和凋亡。进行裸鼠异种移植实验以评估 CIT 敲低 Eca-109 细胞的致瘤性。对转染 LV-shCIT 或 LV-shNC 的 Eca-109 细胞进行微阵列分析以及随后的 Ingenuity Pathway Analysis (IPA)，以鉴定 CIT 相关的差异表达基因 (DEG) 和信号通路。此外，利用 ESCC 的临床样本验证了关键 DEG 的表达。香橼激酶（CIT）在食管鳞癌组织和细胞系中高表达。在体外，CIT 的敲低可抑制 Eca-109 细胞增殖并促进细胞凋亡。此外，CIT 敲低显着降低了 Eca-109 细胞的体内致瘤性。微阵列和 IPA 分析表明，Rho 家族 GTPases 通路的信号传导显着激活，并且 CIT 与蛋白激酶 AMP 激活的催化亚基 α 1 (PRKAA1)、sequestosome 1 (SQSTM1) 和白细胞介素 6 (IL6) 存在内在相互作用。值得注意的是，ESCC组织中PRKAA1和SQSTM1的表达水平上调，而IL6的表达水平下调。我们的研究结果证实 CIT 在 ESCC 中发挥癌基因的作用。 CIT 可能通过上调 PRKAA1 和 SQSTM1 以及下调 IL6 促进 ESCC 的发展。 Citron 激酶可能作为食管鳞癌的一个有前途的治疗靶点。
This study aimed to investigate the role and potential regulatory mechanism of citron kinase (CIT) in esophageal squamous cell carcinoma (ESCC). Citron kinase (CIT) expression in ESCC tissues was analyzed based on the microarray dataset GSE20347, and CIT expression in ESCC cell lines was analyzed. Eca-109 cells were lentivirally transfected with shRNA-CIT (LV-shCIT) to knock down CIT, followed by investigation of cell proliferation and apoptosis. Nude mouse xenograft experiments were performed to evaluate the tumorigenicity of CIT-knockdown Eca-109 cells. Microarray analysis of Eca-109 cells transfected with LV-shCIT or LV-shNC and subsequent Ingenuity Pathway Analysis (IPA) were performed to identify CIT-related differentially expressed genes (DEGs) and signaling pathways. Furthermore, the expression of key DEGs was validated using the clinical samples of ESCC. Citron kinase (CIT) was highly expressed in ESCC tissues and cell lines. Knockdown of CIT suppressed Eca-109 cell proliferation and promoted apoptosis in vitro. Moreover, CIT knockdown significantly reduced tumorigenicity of Eca-109 cells in vivo. Microarray and IPA analysis showed that signaling by the Rho family GTPases pathway was significantly activated, and CIT intrinsically interacted with the protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), sequestosome 1 (SQSTM1), and interleukin 6 (IL6). Notably, the expression levels of PRKAA1 and SQSTM1 were upregulated in ESCC tissues, while the IL6 expression was downregulated. Our findings confirm that CIT functions as an oncogene in ESCC. CIT may contribute to ESCC development by upregulating PRKAA1 and SQSTM1 as well as downregulating IL6. Citron kinase may serve as a promising therapeutic target for ESCC.