Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965Research in context

Autor: Jun Lu, Ling Zhu, Luo-ping Zheng, Qiang Cui, He-huan Zhu, Hu Zhao, Zhou-ji Shen, Hui-yue Dong, Shu-shang Chen, Wei-zhen Wu, Jian-ming Tan
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: EBioMedicine, Vol 34, Iss , Pp 85-93 (2018)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2018.07.034
Popis: Background: Uncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers. Methods: mRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model. Findings: ULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (p
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