Jiang Li, Zhang Jinghui, Hu Naifeng, Liu Aichun, Zhu Hailong, Li Lianqiao, Tian Yuyang, Chen Xue, Quan Lina
a Department of Hematology, Harbin Medical University Cancer Hospital, Harbin 150080, People's Republic of China.
b Department of Internal Medicine, Harbin Fourth Hospital, Harbin 150026, People's Republic of China.
Biochem Cell Biol. 2018 Dec;96(6):786-796. doi: 10.1139/bcb-2017-0345. Epub 2018 May 17.
Casein kinase II subunit alpha (CK2α) is highly expressed in many malignant tumor tissues, including lymphomas and leukemia. To investigate the role of CK2α in cell proliferation and apoptosis of malignant lymphomas and leukemia, 2 lymphoma cell lines and one leukemia cell line were infected with CK2α shRNA lentivirus or negative control shRNA lentivirus, and stably infected cell lines were established. Real-time PCR and Western blot results showed that the mRNA and protein levels of CK2α were significantly reduced in CK2α knockdown cells. The tetrazolium-based colorimetric (MTT) assay found that down-regulation of CK2α inhibited the proliferation of these cells. Flow cytometry analysis showed that inhibition of CK2α induced cell cycle arrest and apoptosis of lymphoma and leukemia cells. In accordance with these, down-regulation of CK2α also reduced the protein levels of proliferating cell nuclear antigen (PCNA), cyclinD1, and bcl-2, and increased the protein expression of bax, cleaved caspase-3, cleaved caspase-9, and cleaved poly(ADP ribose) polymerase (PARP). Moreover, knockdown of CK2α impeded the growth of xenograft tumors in vivo. In summary, our study revealed that CK2α may contribute to the development of malignant lymphoma and leukemia, and serve as the therapeutic target of these malignant tumors.
酪蛋白激酶IIα亚基（CK2α）在包括淋巴瘤和白血病在内的许多恶性肿瘤组织中高表达。为了研究CK2α在恶性淋巴瘤和白血病细胞增殖及凋亡中的作用，用CK2α短发夹RNA慢病毒或阴性对照短发夹RNA慢病毒感染2种淋巴瘤细胞系和1种白血病细胞系，并建立稳定感染的细胞系。实时定量聚合酶链反应（Real-time PCR）和蛋白质免疫印迹（Western blot）结果显示，在CK2α基因敲低的细胞中，CK2α的信使核糖核酸（mRNA）和蛋白质水平显著降低。基于四氮唑的比色法（MTT）检测发现，CK2α的下调抑制了这些细胞的增殖。流式细胞术分析表明，抑制CK2α可诱导淋巴瘤和白血病细胞的细胞周期停滞和凋亡。与此一致的是，CK2α的下调还降低了增殖细胞核抗原（PCNA）、细胞周期蛋白D1和bcl-2的蛋白质水平，并增加了bax、裂解的半胱天冬酶-3、裂解的半胱天冬酶-9和裂解的聚（ADP核糖）聚合酶（PARP）的蛋白质表达。此外，CK2α的基因敲低阻碍了体内异种移植肿瘤的生长。总之，我们的研究表明，CK2α可能促进恶性淋巴瘤和白血病的发展，并可作为这些恶性肿瘤的治疗靶点。
