Cell cycle kinases (AUKA, CDK1, PLK1) are prognostic biomarkers and correlated with tumor-infiltrating leukocytes in HBV related HCC

Islam, Baitul; Yu, Haiyang; Duan, Tian-Qi; Pan, Jianke; Li, Min; Zhang, Ru-Qi; Masroor, Matiullah; Huang, Jufang

doi:10.1080/07391102.2022.2164056

Cited by 6 publications

(14 citation statements)

References 44 publications

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“…32,33 A recent study showed that the up-regulation of CDK1 expression was significantly related to the poor prognosis of liver cancer patients. 34 Besides, we found that the protein products of many genes in the therapeutic network are FDA-approved drug targets. Through a query in DrugBank, it was found that among the 15 hub genes, there were some targets with corresponding approved inhibitors, such as hesperidin (AURKB), 35 ribociclib (CDK4/6), 36 fostamatinib (CHEK1), 37 proving that these targets are not undruggable targets but instead have certain druggable properties.…”

Section: Discussionmentioning

confidence: 96%

Validation of Core Ingredients and Molecular Mechanism of Cinobufotalin Injection Against Liver Cancer

Chen,

Li,

Xue

et al. 2024

DDDT

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Cinobufotalin injection has obvious curative effects on liver cancer patients with less toxicity and fewer side effects than other therapeutic approaches. However, the core ingredients and mechanism underlying these anti-liver cancer effects have not been fully clarified due to its complex composition. Methods: Multidimensional network analysis was used to screen the core ingredients, key targets and pathways underlying the therapeutic effects of cinobufotalin injection on liver cancer, and in vitro and in vivo experiments were performed to confirm the findings. Results: By construction of ingredient networks and integrated analysis, eight core ingredients and ten key targets were finally identified in cinobufotalin injection, and all of the core ingredients are tightly linked with the key targets, and these key targets are highly associated with the cell cycle-related pathways, supporting that both cinobufotalin injection and its core ingredients exert antiliver cancer roles by blocking cell cycle-related pathways. Moreover, in vitro and in vivo experiments confirmed that either cinobufotalin injection or one of its core ingredients, cinobufagin, significantly inhibited cell proliferation, colony formation, cell cycle progression and xenograft tumor growth, and the key target molecules involved in the cell cycle pathway such as CDK1, CDK4, CCNB1, CHEK1 and CCNE1, exhibit consistent changes in expression after treatment with cinobufotalin injection or cinobufagin. Interestingly, some key targets CDK1, CDK4, PLK1, CHEK1, TTK were predicted to bind with multiple of core ingredients of cinobufotalin injection, and the affinity between one of the critical ingredients cinobufagin and key target CDK1 was further confirmed by SPR assay. Conclusion: Cinobufotalin injection was confirmed to includes eight core ingredients, and they play therapeutic effects in liver cancer by blocking cell cycle-related pathways, which provides important insights for the mechanism of cinobufotalin injection antagonizing liver cancer and the development of novel small molecule anti-cancer drugs.

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Section: Discussionmentioning

confidence: 96%

Validation of Core Ingredients and Molecular Mechanism of Cinobufotalin Injection Against Liver Cancer

Chen,

Li,

Xue

et al. 2024

DDDT

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“…Overexpression of AURKA/B, CDK1, and PLK1 has been reported in several malignant tumors, including HCC [30,32,33]. A recent study has demonstrated that the overexpression of AURKA, CDK1, and PLK1 is positively correlated with tumor grades and stage.…”

Section: Discussionmentioning

confidence: 99%

“…Thereby, these genes may be used as prognostic biomarkers for HBV-induced HCC. Furthermore, there is a strong correlation between high expression of AURKA, CDK1, and PLK1 and the infiltration of immune cells [33]. The coordinated overexpression of FOXM1 and AURKA has been linked to the worst overall survival in sorafenib-treated patients with HCC [34].…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative Activity of N-Acylhydrazone Derivative on Hepatocellular Carcinoma Cells Involves Transcriptional Regulation of Genes Required for G2/M Transition

Andrade,

Pauli,

Pressete

et al. 2024

Biomedicines

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Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage. The drug arsenal used in systemic therapy for HCC is very limited. Multikinase inhibitors sorafenib (Nexavar®) and lenvatinib (Lenvima®) have been used as first-line drugs with modest therapeutic effects. In this scenario, it is imperative to search for new therapeutic strategies for HCC. Herein, the antiproliferative activity of N-acylhydrazone derivatives was evaluated on HCC cells (HepG2 and Hep3B), which were chemically planned on the ALL-993 scaffold, a potent inhibitor of vascular endothelial growth factor 2 (VEGFR2). The substances efficiently reduced the viability of HCC cells, and the LASSBio-2052 derivative was the most effective. Further, we demonstrated that LASSBio-2052 treatment induced FOXM1 downregulation, which compromises the transcriptional activation of genes required for G2/M transition, such as AURKA and AURKB, PLK1, and CDK1. In addition, LASSBio-2052 significantly reduced CCNB1 and CCND1 expression in HCC cells. Our findings indicate that LASSBio-2052 is a promising prototype for further in vivo studies.

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“…Further studies may reveal differences in wound healing mechanisms between ruminants and other animals, such as humans and mice. PLK1 is a key regulator of cell mitosis and is overexpressed in various of cancers ( 22 ). Song et al found that interference with PLK1 by siRNA in wound healing and invasion experiments can significantly inhibit cell migration and invasion ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling identifies differentially expressed genes and related pathways associated with wound healing and cuproptosis-related genes in Ganxi goats

et al. 2023

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IntroductionWound healing is very important for the maintenance of immune barrier integrity, which has attracted wide attention in past 10 years. However, no studies on the regulation of cuproptosis in wound healing have been reported.MethodsIn this study, the skin injury model was constructed in Gnxi goats, and the function, regulatory network and hub genes of the skin before and after the injury were comprehensively analyzed by transcriptomics.ResultsThe results showed that there were 1,438 differentially expressed genes (DEGs), genes up-regulated by 545 and genes down-regulated by 893, which were detected by comparing day 0 and day 5 posttraumatic skin. Based on GO-KEGG analysis, DEGs that were up-regulated tended to be enriched in lysosome, phagosome, and leukocyte transendothelial migration pathways, while down-regulated DEGs were significantly enriched in adrenergic signaling in cardiomyocytes and calcium signaling pathway. There were 166 overlapped genes (DE-CUGs) between DEGs and cuproptosis-related genes, with 72 up-regulated DE-CUGs and 94 down-regulated DE-CUGs. GOKEGG analysis showed that up-regulated DE-CUGs were significantly enriched in ferroptosis, leukocyte transendothelial migration and lysosome pathways, while down-regulated DE-CUGs were significantly enriched in Apelin signaling pathway and tyrosine metabolism pathways. By constructing and analyzing of protein–protein interaction (PPI) networks of DEGs and DE-CUGs, 10 hub DEGs (ENSCHIG00000020079, PLK1, AURKA, ASPM, CENPE, KIF20A, CCNB2, KIF2C, PRC1 and KIF4A) and 10 hub DE-CUGs (MMP2, TIMP1, MMP9, MMP14, TIMP3, MMP1, EDN1, GCAT, SARDH, and DCT) were obtained, respectively.DiscussionThis study revealed the hub genes and important wound healing pathways in Ganxi goats, and identified the correlation between wound healing and cuproptosis for the first time, and found that MMP2, TIMP1, MMP9, and EDN1 were the core genes associated. This study enriched the transcriptome data of wound healing in Ganxi goats and expanded the research direction of cuproptosis.

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Cell cycle kinases (AUKA, CDK1, PLK1) are prognostic biomarkers and correlated with tumor-infiltrating leukocytes in HBV related HCC

Cited by 6 publications

References 44 publications

Validation of Core Ingredients and Molecular Mechanism of Cinobufotalin Injection Against Liver Cancer

Validation of Core Ingredients and Molecular Mechanism of Cinobufotalin Injection Against Liver Cancer

Antiproliferative Activity of N-Acylhydrazone Derivative on Hepatocellular Carcinoma Cells Involves Transcriptional Regulation of Genes Required for G2/M Transition

Transcriptomic profiling identifies differentially expressed genes and related pathways associated with wound healing and cuproptosis-related genes in Ganxi goats

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