SIRT7 Downregulation Promotes Breast Cancer Metastasis Via LAP2α-Induced Chromosomal Instability

Huo, Qin; Chen, Siqi; Liu, Sian; Quan, Chuntao; Wang, Yue; Xie, Ni

doi:10.7150/ijbs.75340

Cited by 7 publications

(4 citation statements)

References 50 publications

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“…Particularly noteworthy is the fact that SIRT7 is the sole sirtuin that exhibits localization in the nucleolus of cells, and its absence in mice leads to genomic instability and accelerated aging [ 33 ]. Although SIRT7 is overexpressed in various types of tumors, there is inconsistent evidence in the literature regarding its role in tumor development [ 34 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

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DDX3X interacts with SIRT7 to promote PD-L1 expression to facilitate PDAC progression

Zhao,

Zhu,

Zou

et al. 2024

Oncogenesis

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Pancreatic ductal adenocarcinoma (PDAC) is recognized as the most aggressive and fatal malignancy. A previous study reported that PDAC patients who exhibit elevated levels of DDX3X have a poor prognosis and low overall survival rate. However, the underlying molecular mechanism remains unclear. This study aimed to investigate the specific roles of DDX3X in PDAC. Multiple bioinformatics analyses were used to evaluate DDX3X expression and its potential role in PDAC. In vitro and in vivo studies were performed to assess the effects of DDX3X on PDAC cell growth. Furthermore, Western blotting, quantitative PCR, immunohistochemistry, immunofluorescence, mass spectrometry, coimmunoprecipitation and multiplexed immunohistochemical staining were conducted to identify the specific regulatory mechanism in PDAC. The results verified that DDX3X expression is notably upregulated in the tumor tissue vs. normal tissue of PDAC patients. DDX3X knockdown markedly suppressed the proliferation, invasion and migration of PDAC cells in vitro and inhibited tumor growth in vivo. Conversely, overexpression of DDX3X induced the opposite effect. Further studies supported that the DDX3X protein can associate with sirtuin 7 (SIRT7) to stimulate PDAC carcinogenesis and progression. Furthermore, SIRT7 inhibition significantly impeded DDX3X-mediated tumor growth both ex vivo and in vivo. The results also revealed that programmed death ligand 1 (PD-L1) expression is positively correlated with DDX3X expression. These results reveal significant involvement of the DDX3X-SIRT7 axis in the initiation and advancement of PDAC and offer previously undiscovered therapeutic options for PDAC management.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, SIRT7 plays a crucial role in promoting liver cancer metastasis [ 35 ]. Conversely, a subsequent investigation revealed that the repression of SIRT7 may trigger breast cancer metastasis [ 34 ]. At the molecular scale, it has been acknowledged that SIRT7 interacts with and stimulates the deacetylation process of P53 [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

DDX3X interacts with SIRT7 to promote PD-L1 expression to facilitate PDAC progression

Zhao,

Zhu,

Zou

et al. 2024

Oncogenesis

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“…For instance, Yu et al demonstrated that SIRT7 overexpression exhibits oncogenic effects and serves as a prognostic factor in colorectal cancer (Yu et al, 2014). Additionally, SIRT7 interacts with LAP2α in breast cancer, and inhibition of the SIRT7/LAP2α axis represents a potential therapeutic strategy for preventing breast cancer metastasis (Huo et al, 2023). SIRT7 is an NAD + -dependent A novel mechanism of p53 knockout regulating cisplatin chemotherapy resistance through SIRT7/RRM2 K283Cr /cleaved-PARP1 and cleaved-caspase3 axis-mediated apoptosis reduction in colon cancer.…”

Section: Discussionmentioning

confidence: 99%

p53 deficiency mediates cisplatin resistance by upregulating RRM2 and crotonylation of RRM2K283 through the downregulation of SIRT7

Sun,

Li,

Wang

et al. 2024

Front. Mol. Biosci.

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p53 deficiency plays a crucial role in chemotherapy resistance through various biological events, including posttranslational modifications (PTMs). Recently, lysine crotonylation (Kcr) has been shown to play a vital role in cancer progression. However, the global p53-regulated crotonylome and the function of these altered Kcr proteins after p53 deficiency remain unclear. In this study, we used a SILAC-based quantitative crotonylome to identify 3,520 Kcr in 1924 crotonylated proteins in response to p53 knockout. We found that increased crotonylation of RRM2 at K283 (RRM2K283Cr) in the presence of p53 deficiency promoted HCT116 cell resistance to cisplatin. We discovered that SIRT7 could be the decrotonylase of RRM2 and was downregulated after p53 knockout, resulting in increased RRM2K283Cr. Mechanistically, p53 deficiency inhibited cell apoptosis by upregulating RRM2 protein expression and RRM2K283Cr-mediated cleaved-PARP1 and cleaved-caspase3 expression, and SIRT7 was downregulated to upregulate crotonylation of RRM2 upon p53 deficiency. In conclusion, our results indicated that p53 deficiency plays a malignant role in colon cancer resistance to cisplatin therapy by regulating RRM2 protein and RRM2K283Cr expression. Our findings provide a novel therapeutic target against p53-deficient cancer.

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“…As with the other SIRTs, Citrus flavonoids h been investigated for their effects on SIRT7. In this regard, it has been reported that It has been reported that SIRT7 plays a key role in the regulation of chronic inflammation [196], as well as in different kinds of cancer, including breast cancer [197], melanoma [198], and ovarian cancer [199]. As with the other SIRTs, Citrus flavonoids have been investigated for their effects on SIRT7.…”

Section: Sirt7mentioning

confidence: 99%

Sirtuins as Players in the Signal Transduction of Citrus Flavonoids

Lombardo,

Russo,

Maugeri

et al. 2024

IJMS

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Sirtuins (SIRTs) belong to the family of nicotine adenine dinucleotide (NAD+)-dependent class III histone deacetylases, which come into play in the regulation of epigenetic processes through the deacetylation of histones and other substrates. The human genome encodes for seven homologs (SIRT1-7), which are localized into the nucleus, cytoplasm, and mitochondria, with different enzymatic activities and regulatory mechanisms. Indeed, SIRTs are involved in different physio-pathological processes responsible for the onset of several human illnesses, such as cardiovascular and neurodegenerative diseases, obesity and diabetes, age-related disorders, and cancer. Nowadays, it is well-known that Citrus fruits, typical of the Mediterranean diet, are an important source of bioactive compounds, such as polyphenols. Among these, flavonoids are recognized as potential agents endowed with a wide range of beneficial properties, including antioxidant, anti-inflammatory, hypolipidemic, and antitumoral ones. On these bases, we offer a comprehensive overview on biological effects exerted by Citrus flavonoids via targeting SIRTs, which acted as modulator of several signaling pathways. According to the reported studies, Citrus flavonoids appear to be promising SIRT modulators in many different pathologies, a role which might be potentially evaluated in future therapies, along with encouraging the study of those SIRT members which still lack proper evidence on their support.

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SIRT7 Downregulation Promotes Breast Cancer Metastasis Via LAP2α-Induced Chromosomal Instability

Cited by 7 publications

References 50 publications

DDX3X interacts with SIRT7 to promote PD-L1 expression to facilitate PDAC progression

DDX3X interacts with SIRT7 to promote PD-L1 expression to facilitate PDAC progression

p53 deficiency mediates cisplatin resistance by upregulating RRM2 and crotonylation of RRM2K283 through the downregulation of SIRT7

Sirtuins as Players in the Signal Transduction of Citrus Flavonoids

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