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

Abstract

Summary 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.

KYNU, a novel potential target that underpins CD44‐promoted breast tumour cell invasion

“…11 KYNU is involved in various inflammatory and cardiovascular diseases, in addition to several types of cancers, acting via different pathways ( Figure 1). [12][13][14][15] Here we discuss the findings, from the literature, supporting the hypothesis that KYNU is a transcriptional target of CD44 as well as known signalling pathways linking the activation of CD44 by HA to the transactivation of KYNU in promoting breast tumour cell invasion.…”

MicroRNA‑451a prevents cutaneous squamous cell carcinoma progression via the 3‑phosphoinositide‑dependent protein kinase‑1‑mediated PI3K/AKT signaling pathway

“…The results revealed that the 'PI3K-Akt signaling pathway' was enriched (data not shown; Fig. 5A), which has been reported to be associated with the malignant behavior of cSCC cells (26,27). Moreover, the PDPK1 gene was located upstream of the PI3K/AKT signaling pathway (Fig.…”

<p>Wogonoside Attenuates Cutaneous Squamous Cell Carcinoma by Reducing Epithelial–Mesenchymal Transition/Invasion and Cancer Stem-Like Cell Property</p>

“…Ci et al found that downregulation of kynureninase inhibited proliferation of cSCC and restrained the PI3K/AKT pathway. 43 Li et al reported that microRNA-374 affected the proliferation, migration, invasion and apoptosis of cSCC cells by targeting Gadd45a through the p53 signaling pathway. 44 However, the mechanism of wogonoside on cSCC has not been clarified.…”