Department of, Dermatology, First Affiliated Hospital of Wannan Medical College, Wuhu, China.
Department of, Burn and Plastic Surgery, First Affiliated Hospital of Wannan Medical College, Wuhu, China.
Clin Exp Dermatol. 2020 Mar;45(2):194-201. doi: 10.1111/ced.14072. Epub 2019 Sep 26.
The protein kynureninase (KYNU) has recently been reported to participate in the pathological processes of various diseases.
To explore the expression and the biological function of KYNU in cutaneous squamous cell carcinoma (cSCC).
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.
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.
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.
蛋白色氨酸酶（KYNU）最近被报道参与多种疾病的病理过程。
探索 KYNU 在皮肤鳞状细胞癌（cSCC）中的表达和生物学功能。
基于基因表达综合数据库和 Oncomine 数据库首次评估 KYNU 在 cSCC 细胞系和组织中的表达。定量逆转录-PCR 用于确定 cSCC 细胞系中 KYNU 的 mRNA 表达。使用小干扰 RNA（siRNA）沉默 KYNU。通过细胞计数试剂盒-8 测定、划痕愈合和 Transwell 测定确定 KYNU 对 cSCC 细胞生长和迁移的影响，并用 Western blot 测定 KYNU、AKT、磷酸肌醇 3-激酶（PI3K）、磷酸化（p）-AKT 和 p-PI3K 的蛋白表达。
KYNU 在 cSCC 组织和细胞系中显著上调。使用 siRNA 敲低 KYNU 可明显抑制 SCL-1 细胞的增殖、迁移和侵袭能力（P<0.01）。Western blot 显示沉默 KYNU 后 AKT 和 PI3K 的磷酸化明显受到抑制。与对照组相比，si-KYNU 组中 p-AKT/AKT 和 p-PI3K/PI3K 的比值明显降低。
耗尽 KYNU 可抑制 cSCC 细胞的生长，可能通过调节 PI3K/AKT 通路。这些数据表明 KYNU 在 cSCC 的恶性进展中起着关键作用，可被视为治疗 cSCC 的有前途的治疗靶点。
