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TIPE1-mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-06-25 , DOI: 10.1111/jcmm.15550
Yongliang Liu 1 , Xiangqin Qi 2 , Zhenan Zhao 1 , Daoliang Song 1 , Lianqing Wang 3 , Qiaoli Zhai 3 , Xiaoning Zhang 3 , Peiqing Zhao 3 , Xinxin Xiang 3
Affiliation  

Recent studies have shown that tumour necrosis factor‐α–induced protein 8 like‐1(TIPE1) plays distinct roles in different cancers. TIPE1 inhibits tumour proliferation and metastasis in a variety of tumours but acts as an oncogene in cervical cancer. The role of TIPE1 in nasopharyngeal carcinoma (NPC) remains unknown. Interestingly, TIPE1 expression was remarkably increased in NPC tissue samples compared to adjacent normal nasopharyngeal epithelial tissue samples in our study. TIPE1 expression was positively correlated with that of the proliferation marker Ki67 and negatively correlated with patient lifespan. In vitro, TIPE1 inhibited autophagy and induced cell proliferation in TIPE1‐overexpressing CNE‐1 and CNE‐2Z cells. In addition, knocking down TIPE1 expression promoted autophagy and decreased proliferation, whereas overexpressing TIPE1 increased the levels of pmTOR, pS6 and P62 and decreased the level of pAMPK and the LC3B. Furthermore, the decrease in autophagy was remarkably rescued in TIPE1‐overexpressing CNE‐1 and CNE‐2Z cells treated with the AMPK activator AICAR. In addition, TIPE1 promoted tumour growth in BALB/c nude mice. Taken together, results indicate that TIPE1 promotes NPC progression by inhibiting autophagy and inducing cell proliferation via the AMPK/mTOR signalling pathway. Thus, TIPE1 could potentially be used as a valuable diagnostic and prognostic biomarker for NPC.

中文翻译:

TIPE1介导的自噬抑制通过AMPK / mTOR信号通路促进鼻咽癌细胞增殖。

最近的研究表明,肿瘤坏死因子-α诱导的蛋白8 like-1(TIPE1)在不同的癌症中起不同的作用。TIPE1抑制多种肿瘤中的肿瘤增殖和转移,但在宫颈癌中起癌基因的作用。TIPE1在鼻咽癌(NPC)中的作用仍然未知。有趣的是,在我们的研究中,与相邻的正常鼻咽上皮组织样品相比,NPC组织样品中TIPE1表达显着增加。TIPE1表达与增殖标志物Ki67呈正相关,与患者寿命呈负相关。在体外,TIPE1在过表达TIPE1的CNE-1和CNE-2Z细胞中抑制自噬并诱导细胞增殖。此外,敲低TIPE1表达可促进自噬并减少增殖,而过表达TIPE1则增加pmTOR,pS6和P62的水平,并降低pAMPK和LC3B的水平。此外,在用AMPK激活剂AICAR处理的TIPE1过表达的CNE-1和CNE-2Z细胞中,自噬的减少得到了明显的挽救。此外,TIPE1促进了BALB / c裸鼠的肿瘤生长。两者合计,结果表明TIPE1通过抑制自噬并通过AMPK / mTOR信号通路诱导细胞增殖来促进NPC进程。因此,TIPE1可以潜在地用作NPC的有价值的诊断和预后生物标志物。TIPE1促进BALB / c裸鼠的肿瘤生长。两者合计,结果表明TIPE1通过抑制自噬并通过AMPK / mTOR信号传导途径诱导细胞增殖来促进NPC进程。因此,TIPE1可以潜在地用作NPC的有价值的诊断和预后生物标志物。TIPE1促进BALB / c裸鼠的肿瘤生长。两者合计,结果表明TIPE1通过抑制自噬并通过AMPK / mTOR信号传导途径诱导细胞增殖来促进NPC进程。因此,TIPE1可以潜在地用作NPC的有价值的诊断和预后生物标志物。
更新日期:2020-08-11
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