<scp>SIRT</scp>5 inhibits peroxisomal<scp>ACOX</scp>1 to prevent oxidative damage and is downregulated in liver cancer

Chen, Xiu Fei; Tian, Meng; Sun, Ren Qiang; Zhang, Meng Li; Zhou, Li; Jin, Lei; Chen, Lei Lei; Zhou, Wen; Duan, Kun-Long; Chen, Yu-Jia; Gao, Chao; Cheng, Zhou Li; Wang, Fang; Zhang, Jin Ye; Sun, Yi; Yu, Hong; Zhao, Yuzheng; Yang, Yi; Liu, Wei‐Ren; Shi, Ying; Xiong, Yue; Guan, Kun Liang; Ye, Dan

doi:10.15252/embr.201745124

Cited by 204 publications

(152 citation statements)

References 66 publications

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“…Additionally, patients with pathological grade II, a high clinical stage (III+IV), a TP53 mutation and those who received chemotherapy experienced improved OS, further indicating that increased SIRT3 expression predicts prolonged OS. SIRT5 has been reported to possess dual roles in the regulation of various types of carcinoma, suggesting that SIRT5 acts as a tumor suppressor in hepatic cancer by inhibiting acyl-CoA oxidase 1 (42). However, SIRT5 has also been demonstrated to function as an oncogene in the carcinogenesis of colorectal cancer (CRC), potentially by stimulating glutamine metabolism through the activation of dehydrogenase 1 during the tricarboxylic-acid cycle in CRC cells (43).…”

Section: Discussionmentioning

confidence: 99%

Associations of sirtuins with clinicopathological variables and prognosis in human ovarian cancer

Chen

et al. 2020

Oncol Lett

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Ovarian cancer (OC) is the fifth most frequent cause of cancer-associated mortality worldwide, and is accompanied by asymptomatic progression. Sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide-dependent protein deacetylases, comprising seven members (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7). Accumulating evidence has demonstrated that SIRTs act as prognostic estimators in certain types of cancer such as lung cancer, prostate cancer, gastric cancer, breast cancer and colorectal cancer. However, it remains unknown whether individual SIRTs can serve as independent prognostic factors in OC. In the present study, the Kaplan-Meier plotter online database was utilized to examine the prognostic values of SIRT mRNA expression in patients with OC. The results demonstrated that the overexpression of SIRT3, SIRT5, SIRT6 and SIRT7 mRNAs was associated with a good prognosis in patients, whereas elevated mRNA levels of SIRT1 and SIRT4 indicated poor survival in patients with OC. In addition, among the favorable predictors, SIRT3, SIRT5, SIRT6 and SIRT7 overexpression were associated with overall survival (OS), according to clinical characteristics, such as histological classification, clinical stage, pathology grade, drug therapy and tumor protein p53 mutation status in patients with OC. Similarly, SIRT4 mRNA overexpression was associated with poor OS in pathological grade III cancer. High SIRT1 and SIRT4 expression were associated with unfavorable OS at all clinical stages. Furthermore, SIRT1 and SIRT4 were negatively associated with OS in drug-treated patients. In summary, the present study demonstrated that the SIRT family is associated with the prognosis of human OC, suggesting that individual SIRTs may also act as prognostic predictors in patients.

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Section: Discussionmentioning

confidence: 99%

Associations of sirtuins with clinicopathological variables and prognosis in human ovarian cancer

Chen

et al. 2020

Oncol Lett

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“…Moreover, the SIRT5 gene frequently shows an increase in duplication in specific cancer types, including uterine cancer, breast cancer, cutaneous and uveal melanomas, lung cancer, and lymphoma [150]. However, high SIRT5 expression is interrelated with a favorable prognosis for patients with HCC; the downregulation of SIRT5 is correlated with high ACOX1 succinylation and activity and poor survival in HCC patients [151]. Clearly, further studies are required to examine the possible involvement of SIRT5 in tumorigenesis.…”

Section: Sirtuins In Tumorigenesismentioning

confidence: 99%

The Roles of Sirtuin Family Proteins in Cancer Progression

Zhao

Hou

et al. 2019

Cancers

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Sirtuin family members are characterized by either mono-ADP-ribosyltransferase or deacylase activity and are linked to various cancer-related biological pathways as regulators of transcriptional progression. Sirtuins play fundamental roles in carcinogenesis and maintenance of the malignant phenotype, mainly participating in cancer cell viability, apoptosis, metastasis, and tumorigenesis. Although sirtuin family members have a high degree of homology, they may play different roles in various kinds of cancer. This review highlights their fundamental roles in tumorigenesis and cancer development and provides a critical discussion of their dual roles in cancer, namely, as tumor promoters or tumor suppressors.

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“…In fact, dy-regulations of peroxisomal enzymes and/or their effects were shown in numerous tumor types including prostate cancer (Ko et al, 2018), colorectal carcinoma (Lakis et al, 2010), liver cancer (Lu et al, 2015;Chen et al, 2018), oral squamous cell carcinoma (Lai et al, 2018), pancreatic cancer (Deplanque et al, 2015), breast cancer (Keller et al, 1993), and lymphoma (Zheng et al, 2019). However, there was no systemic study of peroxisomes in lung cancer.…”

Section: Introductionmentioning

confidence: 99%

HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

et al. 2020

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To explore the potential functions and clinical significances of peroxisomes during lung cancer development and progression, we investigated the expressional profiles of peroxisome pathway genes and their correlations with clinical features in nonsmall cell lung cancer (NSCLC). The RNA-seq data of NSCLC including lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients with their clinical information were downloaded from The Cancer Genome Atlas (TCGA). Gene expression comparisons between tumor and normal samples were performed with edgeR package in R software and the results of the 83 peroxisome pathway genes were extracted. Through Venn diagram analysis, 38 common differentially expressed peroxisome pathway genes (C-DEPGs) in NSCLC were identified. Principal components analysis (PCA) was performed and the 38 C-DEPGs could discriminate NSCLC tumors from the non-tumor controls well. Through Kaplan-Meier survival and Cox regression analyses, 11 of the C-DEPGs were shown to have prognostic effects on NSCLC overall survival (OS) and were considered as key C-DEPGs (K-DEPGs). Through Oncomine, Human Protein Atlas (HPA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), three K-DEPGs (HSD17B4, ACAA1, and PXMP4) were confirmed to be down-regulated in NSCLC at both mRNA and protein level. Their dyregulation mechanisms were revealed through their correlations with their copy number variations and methylation status. Their potential functions in NSCLC were explored through their NSCLC-specific co-expression network analysis, their correlations with immune infiltrations, immunomodulator gene expressions, MKI67 expression and their associations with anti-cancer drug sensitivity. Our findings suggested that HSD17B4, ACAA1, and PXMP4 might be new markers for NSCLC diagnosis and prognosis and might provide new clues for NSCLC treatment.

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SIRT5 inhibits peroxisomalACOX1 to prevent oxidative damage and is downregulated in liver cancer

Cited by 204 publications

References 66 publications

Associations of sirtuins with clinicopathological variables and prognosis in human ovarian cancer

Associations of sirtuins with clinicopathological variables and prognosis in human ovarian cancer

The Roles of Sirtuin Family Proteins in Cancer Progression

HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

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