Increased DKC1 expression in glioma and its significance in tumor cell proliferation, migration and invasion
Increased DKC1 expression in glioma and its significance in tumor cell proliferation, migration and invasion
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胶质瘤中DKC1表达增加及其在肿瘤细胞增殖、迁移和侵袭中的意义
DOI：
10.1007/s10637-019-00748-w
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发表时间：
2019-12-01
影响因子：
3.4
通讯作者：
You, Yong-ping
中科院分区：
文献类型：
--
作者：
Miao, Fa-an;Chu, Kun;You, Yong-ping
先天性角化不良1（DKC 1）基因位于X染色体Xq 28。由DKC 1基因编码的Dyskerin与某些小RNA的形成和端粒酶活性相关。DKC 1中的遗传突变会破坏dyskerin并导致先天性角化不良，其特征在于皮肤缺陷、造血功能衰竭和对癌症的易感性增加。据报道，DKC 1在几种人类癌症中上调，包括肾细胞癌和前列腺癌。Dyskerin在B-慢性淋巴细胞白血病和乳腺癌中表达失调，但其在胶质瘤中的表达和功能尚不清楚。因此，我们被提示收集组织样本并进行细胞实验。我们的研究表明，DKC 1在胶质瘤病理组织中的表达明显高于正常组织。DKC 1染色的增加与世界卫生组织的肿瘤分期有关。DKC 1敲除还通过改变细胞周期相关分子的表达以使其停滞在G1期来显著抑制胶质瘤细胞生长。在transwell小室中，DKC 1敲低的胶质瘤细胞表现出低运动性。与经典的致癌途径一致，与对照组相比，N-cadherin、HIF-1α和MMP 2的表达水平较低。因此，神经胶质瘤中DKC 1上调是常见的，并且是广泛肿瘤生长所必需的。DKC 1下调后胶质瘤细胞系的表型表明其可用作有价值的临床治疗策略。
The dyskeratosis congenita 1 (DKC1) gene is located on the X chromosome at Xq28. Dyskerin encoded by the DKC1 gene is associated with the formation of certain small RNAs and the telomerase activity. Inherited mutations in DKC1 inactivate the dyskerin and causes dyskeratosis congenital, which is characterized by skin defects, hematopoiesis failure, and increased susceptibility to cancer. DKC1 reportedly up-regulates in several human cancers, including renal cell carcinoma and prostate cancer. Dyskerin is deregulated in B-chronic lymphocytic leukemia and breast carcinomas, but its expression and function in glioma have hardly been investigated. Hence, we were prompted to collect tissue samples and implement cell experiments. Our study reveals that DKC1 expression is significantly increased in the pathological tissues of glioma compared with that in normal tissues. The increased staining of DKC1 is related to the World Health Organization stages of tumors. DKC1 knockdown also significantly inhibits glioma cell growth by altering the expression of cell cycle-relative molecules to arrest at the G1 phase. In the transwell chamber, DKC1 knockdown glioma cells exhibit low motility. Consistent with classic oncogenic pathways, N-cadherin, HIF-1α, and MMP2 expression levels are lower compared with those of the control group. Therefore, DKC1 up-regulation in gliomas is common and necessary for extensive tumor growth. The phenotype of glioma cell lines after DKC1 down-regulation suggests its use as a valuable clinical treatment strategy.