PADI3 induces cell cycle arrest via the Sirt2/AKT/p21 pathway and acts as a tumor suppressor gene in colon cancer

Chang, Xiaotian; Chai, Zhengbin; Zou, Jiaorui; Wang, Hongxing; Wang, Yao; Zheng, Yabing; Wu, Hui; Liu, Chunyan

doi:10.20892/j.issn.2095-3941.2019.0065

Cited by 18 publications

(9 citation statements)

References 40 publications

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“…Indeed, SIRT2 deacetylase activity positively regulates the binding of AKT to inositol 1,4,5-triphosphate (PI3K), leading to the activation of the PI3K/AKT pathway, involved in cell proliferation, survival, and apoptosis. In addition, the overexpression of SIRT2 was significantly associated with an increase of AKT phosphorylation in PADI3-expressing HCT116 colon cancer cells [ 56 ]. Interestingly, one of the most abundant flavonoids in Citrus fruits, naringenin, was shown to induce apoptosis in human leukemia THP-1 cells through the down-regulation of AKT and activation of caspase-3 [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

The Anticancer Effect of a Flavonoid-Rich Extract of Bergamot Juice in THP-1 Cells Engages the SIRT2/AKT/p53 Pathway

et al. 2022

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Novel targets are constantly sought to fight hematologic malignancies. In this regard, high levels of SIRT2 expression are associated with unfavorable prognosis of acute myeloid leukemia. The interest in the plant kingdom has allowed the identification of ever-new anti-leukemic agents. Citrus × bergamia (bergamot) was proved to possess anticancer properties, yet no evidence is available regarding leukemia. For the first time, we studied the potential anti-leukemic effect of a flavonoid-rich extract of bergamot juice (BJe) in THP-1 cells, investigating the underlying mechanisms. Our findings showed that BJe reduced THP-1 cell proliferation, without affecting that of primary PBMCs, blocking the cell cycle in S phase and inducing apoptosis. Triggering of both extrinsic and intrinsic apoptotic pathways was witnessed by cleavage of caspase-8 and -9, which in turn activated caspase-3 and PARP. Interestingly, the increased p53 acetylation in THP-1 cells underlies SIRT2 inhibition by BJe, that was proved also in the isolated enzyme. Moreover, BJe hampered SIRT2 also by lowering its gene expression. Finally, BJe reduced AKT phosphorylation, which we hypothesized being the joining link between SIRT2 and p53, that play a pivotal role in BJe-induced cell cycle arrest and apoptosis in THP-1 cells. Our results suggest BJe as a potential anti-leukemic agent, via targeting of the SIRT2/AKT/p53 pathway.

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Section: Discussionmentioning

confidence: 99%

The Anticancer Effect of a Flavonoid-Rich Extract of Bergamot Juice in THP-1 Cells Engages the SIRT2/AKT/p53 Pathway

et al. 2022

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“…FOXG1 mediates cancer cell metastasis via the Wnt/β-catenin pathway in hepatocellular carcinoma (HCC) cells and predicts the outcome of HCC following surgery [ 54 ]. PADI3 promotes cell cycle arrest via Sirt2-AKT-p21 and functions as a tumor suppressor gene in colon cancer [ 55 ]. It is well known that miRNAs can exert regulatory effects on target mRNAs by destabilizing them and inhibiting their translation.…”

Section: Discussionmentioning

confidence: 99%

EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis

Liu

Zhang

et al. 2022

Biomolecules

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Prostate cancer (PCa) is a type of potentially fatal malignant tumor. Immunotherapy has shown a lot of potential for various types of solid tumors, but the benefits have been less impressive in PCa. Enhancer of zeste homolog 2 (EZH2) is one of the three core subunits of the polycomb repressive complex 2 that has histone methyltransferase activity, and the immune effects of EZH2 in PCa are still unclear. The purpose of this study was to explore the potential of EZH2 as a prognostic factor and an immune therapeutic biomarker for PCa, as well as the expression pattern and biological functions. All analyses in this study were based on publicly available databases, mainly containing Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), UCSCXenaShiny, and TISIDB. We performed differential expression analysis, developed a prognostic model, and explored potential associations between EZH2 and DNA methylation modifications, tumor microenvironment (TME), immune-related genes, tumor mutation burden (TMB), tumor neoantigen burden (TNB), and representative mismatch repair (MMR) genes. We also investigated the molecular and immunological characterizations of EZH2. Finally, we predicted immunotherapeutic responses based on EZH2 expression levels. We found that EZH2 was highly expressed in PCa, was associated with a poor prognosis, and may serve as an independent prognostic factor. EZH2 expression in PCa was associated with DNA methylation modifications, TME, immune-related genes, TMB, TNB, and MMR. By gene set enrichment analysis and gene set variation analysis, we found that multiple functions and pathways related to tumorigenesis, progression, and immune activation were enriched. Finally, we inferred that immunotherapy may be more effective for PCa patients with low EZH2 expression. In conclusion, our study showed that EZH2 could be a potentially efficient predictor of prognosis and immune response in PCa patients.

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“…Cells were seeded on a cell slide, and after 24 h of incubation, the cells were treated according to different experiments. The detailed procedure was described previously 22 . In brief, cells were fixed with 4% paraformaldehyde and permeabilized with 0.2% Triton X‐100.…”

Section: Methodsmentioning

confidence: 99%

“…The detailed procedure was described previously. 22 In brief, cells were fixed with 4% paraformaldehyde and permeabilized with 0.2% Triton X-100.…”

Section: Immunocytochemistry (Icc)mentioning

confidence: 99%

Dihydroartemisinin synergistically enhances the cytotoxic effects of oxaliplatin in colon cancer by targeting the PHB2‐RCHY1 mediated signaling pathway

Wang

Zheng

Chai

et al. 2022

Molecular Carcinogenesis

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Dihydroartemisinin (DHA) has recently attracted increasing attention for its low toxicity and high antitumor activity. DHA has been reported to have synergistic anticancer effects with a variety of drugs in the clinic; however, the molecular mechanism by which DHA inhibits tumorigenesis and improves oxaliplatin cytotoxicity in colon cancer cells is still not well understood. In this study, we found that DHA can inhibit cell proliferation and colony formation in a dose-dependent manner. Prohibitin 2 (PHB2) is a potential target by which DHA exerts its antitumor and cytotoxic effects.The function and molecular mechanism of PHB2 in colon cancer tumorigenesis were fully studied to determine the regulatory mechanism between DHA and PHB2. We found that PHB2, a mitochondrial inner membrane scaffold protein, has a higher expression level in colon cancer tissues than in adjacent nontumor tissues and is mainly localized in mitochondria. Overexpression of PHB2 can promote cell proliferation and colony formation in vitro and accelerate tumor growth in vivo. We also found that the expression level of PHB2 was inversely related to the cytotoxicity of DHA and oxaliplatin in colon cancer cells. The molecular mechanism of PHB2 in tumorigenesis and cancer therapy was further studied. The results showed that 20 μM DHA can downregulate PHB2 expression in a ubiquitylation-dependent manner and subsequently block PHB2-induced RCHY1 upregulation and p53 and p21 downregulation. In this process, RCHY1 is necessary for PHB2 to play a tumor-promoting role. Thus,

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PADI3 induces cell cycle arrest via the Sirt2/AKT/p21 pathway and acts as a tumor suppressor gene in colon cancer

Cited by 18 publications

References 40 publications

The Anticancer Effect of a Flavonoid-Rich Extract of Bergamot Juice in THP-1 Cells Engages the SIRT2/AKT/p53 Pathway

The Anticancer Effect of a Flavonoid-Rich Extract of Bergamot Juice in THP-1 Cells Engages the SIRT2/AKT/p53 Pathway

EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis

Dihydroartemisinin synergistically enhances the cytotoxic effects of oxaliplatin in colon cancer by targeting the PHB2‐RCHY1 mediated signaling pathway

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