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Knockdown of MAPK14 inhibits the proliferation and migration of clear cell renal cell carcinoma by downregulating the expression of CDC25B.
Cancer Medicine ( IF 2.9 ) Pub Date : 2019-12-19 , DOI: 10.1002/cam4.2795
Junlong Liu 1 , Xiuyue Yu 1 , Hongyuan Yu 1 , Bitian Liu 2 , Zhe Zhang 1 , Chuize Kong 1 , Zhenhua Li 1
Affiliation  

Mitogen-activated protein kinase 14 (MAPK14), which plays an important role in DNA damage and repair, is activated by various environmental stress and proinflammatory cytokines. It is highly active in a variety of tumors, acting as a tumor promoter or suppressor, but its role in clear cell renal cell carcinoma (ccRCC) has not been elucidated. Cell division cycle 25B (CDC25B) is involved in cell cycle regulation and is highly expressed in many malignant tumors. The transcription levels of MAPK14 and CDC25B in 72 pairs of ccRCC and adjacent healthy tissues from the cancer genome atlas database and the protein expression levels in 66 pairs of clinical samples were analyzed in this study. After MAPK14 was knocked down by small interfering RNA (siRNA), P-MAPK14 and CDC25B protein levels decreased. Subsequently, Western blot and co-immunoprecipitation demonstrated that P-MAPK14 could bind to CDC25B, potentially maintaining its stability. The proliferation and migration of ccRCC cell lines were suppressed by siRNA knockdown of MAPK14, however, that could be partially reversed by the overexpression of CDC25B. These results suggest that downregulation of MAPK14 and P-MAPK14 could inhibit the proliferation and migration of ccRCC by downregulating CDC25B.

中文翻译:

MAPK14的抑制通过下调CDC25B的表达来抑制透明细胞肾细胞癌的增殖和迁移。

在DNA损伤和修复中起重要作用的丝裂原活化蛋白激酶14(MAPK14)被各种环境压力和促炎性细胞因子激活。它在多种肿瘤中均具有很高的活性,可作为肿瘤的启动子或抑制剂,但尚未阐明其在透明细胞肾细胞癌(ccRCC)中的作用。细胞分裂周期25B(CDC25B)参与细胞周期调控,并在许多恶性肿瘤中高表达。本研究分析了来自癌症基因组图谱数据库的72对ccRCC和邻近健康组织中MAPK14和CDC25B的转录水平以及66对临床样品中的蛋白质表达水平。MAPK14被小干扰RNA(siRNA)击倒后,P-MAPK14和CDC25B蛋白水平降低。随后,Western印迹和免疫共沉淀表明P-MAPK14可以与CDC25B结合,从而可能保持其稳定性。ccRCC细胞系的增殖和迁移被MAPK14的siRNA抑制所抑制,但是,这可能被CDC25B的过表达部分逆转。这些结果表明,MAPK14和P-MAPK14的下调可以通过下调CDC25B抑制ccRCC的增殖和迁移。
更新日期:2019-12-20
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