ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer

ALKBH4 促进非小细胞肺癌的肿瘤发生,预后不良

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作者:Kentaro Jingushi #, Masaya Aoki #, Kazuhiro Ueda, Takahiro Kogaki, Masaya Tanimoto, Yuya Monoe, Masayuki Ando, Takuya Matsumoto, Kentaro Minami, Yuko Ueda, Kaori Kitae, Hiroaki Hase, Toshiyuki Nagata, Aya Harada-Takeda, Masatatsu Yamamoto, Kohichi Kawahara, Kazuhiro Tabata, Tatsuhiko Furukawa, Masam

Abstract

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 G1 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.

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