Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of General Thoracic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8520, Japan.
Sci Rep. 2021 Apr 21;11(1):8677. doi: 10.1038/s41598-021-87763-1.
The human AlkB homolog family (ALKBH) of proteins play a critical role in some types of cancer. However, the expression and function of the lysine demethylase ALKBH4 in cancer are poorly understood. Here, we examined the expression and function of ALKBH4 in non-small-cell lung cancer (NSCLC) and found that ALKBH4 was highly expressed in NSCLC, as compared to that in adjacent normal lung tissues. ALKBH4 knockdown significantly induced the downregulation of NSCLC cell proliferation via cell cycle arrest at the G phase of in vivo tumour growth. ALKBH4 knockdown downregulated E2F transcription factor 1 (E2F1) and its target gene expression in NSCLC cells. ALKBH4 and E2F1 expression was significantly correlated in NSCLC clinical specimens. Moreover, patients with high ALKBH4 expression showed a poor prognosis, suggesting that ALKBH4 plays a pivotal tumour-promoting role in NSCLC.
人类 AlkB 同源蛋白家族(ALKBH)在某些类型的癌症中发挥着关键作用。然而,赖氨酸去甲基酶 ALKBH4 在癌症中的表达和功能还知之甚少。在这里,我们研究了 ALKBH4 在非小细胞肺癌(NSCLC)中的表达和功能,发现与相邻的正常肺组织相比,ALKBH4 在 NSCLC 中高表达。ALKBH4 敲低通过体内肿瘤生长的 G 期细胞周期阻滞显著诱导 NSCLC 细胞增殖的下调。ALKBH4 敲低下调了 NSCLC 细胞中的 E2F 转录因子 1(E2F1)及其靶基因的表达。ALKBH4 和 E2F1 在 NSCLC 临床标本中的表达呈显著相关性。此外,ALKBH4 高表达的患者预后较差,提示 ALKBH4 在 NSCLC 中发挥关键的肿瘤促进作用。