A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer

Liu, Yingzhe; Feng, Xueping; Lai, Jinping; Yi, Wei; Yang, Jiu; Du, Tao; Long, Xueying; Zhang, Ye; Xiao, Yuzhong

doi:10.1111/jcmm.14547

Cited by 23 publications

(23 citation statements)

References 21 publications

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“…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.…”

supporting

confidence: 66%

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

Al‐Mansoob

Gupta

Rusyniak

et al. 2021

J Cellular Molecular Medi

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Using a validated tetracycline‐off‐inducible CD44 expression system in mouse model, we have previously demonstrated that the hyaluronan (HA) receptor CD44 promotes breast cancer (BC) metastasis to the liver. To unravel the mechanisms that underpin CD44‐promoted BC cell invasion, RNA samples were isolated from two cell models: (a) a tetracycline (Tet)‐Off‐regulated expression system of the CD44s in MCF‐7 cells and; (b) as a complementary approach, the highly metastatic BC cells, MDA‐MB‐231, were cultured in the presence and absence of 50 µg/mL of HA. Kynureninase (KYNU), identified by Microarray analysis, was up‐regulated by 3‐fold upon induction and activation of CD44 by HA; this finding suggests that KYNU is a potential novel transcriptional target of CD44‐downtstream signalling. KYNU is a pyridoxal phosphate (PLP) dependent enzyme involved in the biosynthesis of NAD cofactors from tryptophan that has been associated with the onset and development of BC. This review will attempt to identify and discuss the findings supporting this hypothesis and the mechanisms linking KYNU cell invasion via CD44.

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supporting

confidence: 66%

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

Al‐Mansoob

Gupta

Rusyniak

et al. 2021

J Cellular Molecular Medi

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“…15 A study by Lauvrak et al revealed that expression of KYNU was notably downregulated in highly aggressive osteosarcoma cells 14 and recently, Liu et al reported that KYNU played a suppressive role in tumour growth and development in breast cancer. 16 Other studies have shown that KYNU was upregulated in psoriasis and its expression was positively correlated with psoriasis severity and inflammation. 12 As KYNU is related to skin disease and cancers, we investigated whether KYNU has an effect on cSCC.…”

Section: Discussionmentioning

confidence: 97%

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

Lyu

et al. 2019

Clin Exp Dermatol

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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.

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“…KYNU is a pyridoxal-5´-phosphate dependent enzyme that catalyzes the cleavage of kynurenine into anthranilic acid (AA) and the cleavage of 3-hydroxykynurenine (3-HK) into 3-hydroxyanthranilic acids (3-HAA) ( Badawy, 2017 ). Drugs have been developed to regulate the expression of KYNU to suppress tumor growth through the Kynurenine pathways, such as in breast cancer ( Liu et al, 2019 ; Liu et al, 2020 ) and melanoma ( Rad et al, 2019 ). It has been demonstrated that TTF2 is able to terminate RNA polymerase II transcription, which has an important function in promoting chromosome segregation and altering protein-DNA interactions ( Jiang and Price, 2004 ; Jiang et al, 2004 ; Cheng et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Construction and Analysis of the Tumor-Specific mRNA–miRNA–lncRNA Network in Gastric Cancer

Zheng

Wang

Zheng³

et al. 2020

Front. Pharmacol.

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Weighted correlation network analysis (WGCNA) is a statistical method that has been widely used in recent years to explore gene co-expression modules. Competing endogenous RNA (ceRNA) is commonly involved in the cancer gene expression regulation mechanism. Some ceRNA networks are recognized in gastric cancer; however, the prognosisassociated ceRNA network has not been fully identified using WGCNA. We performed WGCNA using datasets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) to identify cancer-associated modules. The criteria of differentially expressed RNAs between normal stomach samples and gastric cancer samples were set at the false discovery rate (FDR) < 0.01 and |fold change (FC)| > 1.3. The ceRNA relationships obtained from the RNAinter database were examined by both the Pearson correlation test and hypergeometric test to confirm the mRNA-lncRNA regulation. Overlapped genes were recognized at the intersections of genes predicted by ceRNA relationships, differentially expressed genes, and genes in cancer-specific modules. These were then used for univariate and multivariate Cox analyses to construct a risk score model. The ceRNA network was constructed based on the genes in this model. WGCNAuncovered genes in the green and turquoise modules are those most associated with gastric cancer. Eighty differentially expressed genes were observed to have potential prognostic value, which led to the identification of 12 prognosis-related mRNAs (KIF15, FEN1, ZFP69B, SP6, SPARC, TTF2, MSI2, KYNU, ACLY, KIF21B, SLC12A7, and ZNF823) to construct a risk score model. The risk genes were validated using the GSE62254 and GSE84433 datasets, with 0.82 as the universal cutoff value. 12 genes, 12 lncRNAs, and 35 miRNAs were used to build a ceRNA network with 86 dysregulated lncRNA-mRNA ceRNA pairs. Finally, we developed a 12-gene signature from both prognosis-related and tumorspecific genes, and then constructed a ceRNA network in gastric cancer. Our findings may provide novel insights into the treatment of gastric cancer.

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A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer

Cited by 23 publications

References 21 publications

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

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

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

Construction and Analysis of the Tumor-Specific mRNA–miRNA–lncRNA Network in Gastric Cancer

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