Downregulation of kynureninase restrains cutaneous squamous cell carcinoma proliferation and represses the PI3K/AKT pathway

癌症研究 蛋白激酶B PI3K/AKT/mTOR通路 基底细胞 下调和上调 细胞生长 信号转导 生物 医学 细胞生物学 内科学 基因 生物化学
作者
Chao Ci,Chenguang Wu,Donghao Lyu,Xiaolin Chang,Chiyi He,Wen Yuan Liu,Longjiang Chen,Wei Ding
出处
期刊:Clinical and Experimental Dermatology [Oxford University Press]
卷期号:45 (2): 194-201 被引量:35
标识
DOI:10.1111/ced.14072
摘要

Background The protein kynureninase (KYNU) has recently been reported to participate in the pathological processes of various diseases. Aim To explore the expression and the biological function of KYNU in cutaneous squamous cell carcinoma (cSCC). Methods Expression of KYNU in cSCC cell lines and tissues was firstly evaluated based on the Gene Expression Omnibus and the Oncomine databases. Quantitative reverse transcription–PCR was performed to determine the mRNA expression of KYNU in cSCC cell lines. Small interfering RNA (siRNA) was used for silencing KYNU. The effect of KYNU on the growth and motility of cSCC cells was determined by cell counting kit-8, wound-healing and Transwell assays, and western blotting was used to determine the protein expression of KYNU, AKT, phosphoinositide 3-kinase (PI3K), phosphorylated (p)-AKT and p-PI3K. Results KYNU was significantly upregulated in cSCC tissues and cell lines. Knockdown of KYNU using siRNA noticeably suppressed the proliferation, migration and invasion ability of SCL-1 cells (P < 0.01). Western blotting revealed that phosphorylation of AKT and PI3K was markedly inhibited after silencing KYNU. The ratios of p-AKT/AKT and p-PI3K/PI3K were significantly decreased in the si-KYNU group compared with the control group. Conclusion Depletion of KYNU could inhibit the growth of cSCC cells, possibly through modulating PI3K/AKT pathway. These data indicate that KYNU takes a key part in the malignant progression of cSCC, and could be considered as a promising therapeutic target for cSCC treatment.
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