Anti‑malarial drug dihydroartemisinin downregulates the expression levels of <i>CDK1</i> and <i>CCNB1</i> in liver cancer

Hao, Liyuan; Li, Shenghao; Peng, Qing; Guo, Yinglin; Ji, Jingmin; Zhang, Zhiqin; Xue, Yu; Liu, Yiwei; Shi, Xinli

doi:10.3892/ol.2021.12914

Cited by 21 publications

(22 citation statements)

References 37 publications

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“…Our previous study showed DHA inhibited cell growth in HepG2(Hao et al 2021) and HepG2215 cells (Shi et al 2019). To further study the effect of DHA on liver tumor in vivo , C57BL/6 mice with liver tumors in situ were induced by DEN/TCPOBOP (Li et al 2020, Bergmann et al 2017).…”

Section: Resultsmentioning

confidence: 99%

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Dihydroartemisinin broke immune evasion through YAP1/JAK1/STAT1, 3 pathways to enhance anti-PD-1 therapy in hepatocellular carcinoma

Peng

Shi

et al. 2021

Preprint

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The efficacy of anti-PD-1 therapy is not as expected in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) was overexpressed and activated in HCC. This study aimed to investigate the potential mechanism and inhibitor of YAP1 on immune evasion, and promote anti-PD-1 therapy in HCC. Here, we showed that dihydroartemisinin (DHA), an FDA approved drug, directly suppressed YAP1 expression, leading to break immune evasion in liver tumor niche, characterized by decreased PD-L1 in liver tumor cells and increased CD8+ T cell infiltration. Mechanismly, YAP1 is not only directly related to PD-L1, but also involved in activating the JAK1/STAT1, 3 pathways. Moreover, Yap1 knockout elevated CD4+ and CD8+ T cells in liver tumor niche of Yap1LKO mice. Consistently, verteporfin, YAP1 inhibitor, decreased TGF-β in liver tumor niche and exhausted CD8+ T cells in spleen. Furthermore, DHA combined with anti-PD-1 treatment promoted CD4+ T cell infiltration in the spleen and CD8+ T cells in tumor tissues. Thus, we provide a new combined therapeutic strategy for anti-PD-1 with DHA, a potent YAP1 inhibitor, in HCC.

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Section: Resultsmentioning

confidence: 99%

“…DHA was a derivative of artemisinin extracted from artemisia annua Linn (Guo 2016). Our previous studies showed that DHA inhibited HepG2 (Hao et al 2021) and HepG2215 cells (Shi et al 2019). Meanwhile, some studies suggested that DHA downregulated PD-L1 expression in non-small cell lung cancer (Zhang et al 2020).…”

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confidence: 99%

Dihydroartemisinin broke immune evasion through YAP1/JAK1/STAT1, 3 pathways to enhance anti-PD-1 therapy in hepatocellular carcinoma

Peng

Shi

et al. 2021

Preprint

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“…miR-582-5p directly inhibited the expression of CDK1 and AKT3, and indirectly inhibited the expression of cyclinD1, thereby regulating HCC [9]. Experiments have also con rmed that dihydroartemisinin (DHA) can reduce the expression level of CDK1, thereby inhibiting the proliferation of liver cancer cells [10]. At present, CDK1 is highly expressed in various tumour tissues to varying degrees, and it has been proved that CDK1 can play an important role in lung cancer [11], breast cancer [12], pancreatic cancer [13], colorectal cancer [14] and so on by regulating the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of real hub genes in hepatocellular carcinoma based on weighted gene co-expression network analysis

Yuan

Wang

et al. 2022

CBM

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Background: Hepatocellular Carcinoma (HCC) is one of the most common liver malignancies in the world.With highly invasive biological characteristics and lack of obvious clinical manifestations, hepatocellular Carcinoma usually has a poor prognosis and ranks fourth in cancer mortality. The aetiology and exact molecular mechanism of primary hepatocellular carcinoma are still unclear. This work aims to help identify biomarkers of early HCC diagnosis or prognosis.Results: In this study, Expression data and clinical information of HTSEQ-Counts were downloaded from The Cancer Genome Atlas (TCGA) database, and Gene Expression map GSE121248 was downloaded from Gene Expression Omnibus (GEO). By differentially expressed genes (DEGs) and Weighted Gene coexpression Network Analysis WGCNA searched for modules in the two databases that had the same effect on the biological characteristics of HCC, and extracted the module genes with the highest positive correlation with HCC from two databases, and nally obtained overlapping genes. Then, we performed functional enrichment analysis on the overlapping genes to understand their potential biological functions. The top ten hub genes were screened according to MCC through the String database and Cytoscape software. By survival analysis, high expression of CDK1, CCNA2, CDC20, KIF11, DLGAP5, KIF20A, ASPM, CEP55, TPX2 was associated with poorer overall survival (OS) of HCC patients. The DFS curve was plotted using the online website GEPIA2. Finally, based on the enrichment of these genes in the KEGG pathway, real hub genes were screened out, which were CDK1, CCNA2 and CDC20 respectively.Conclusions: High expression of these three genes was negatively correlated with survival time in HCC, and the expression of CDK1, CCNA2 and CDC20 were signi cantly higher in tumour tissues of HCC patients than in normal liver tissues as veri ed again by the HPA database. All in all, this provides a new feasible target for early and accurate diagnosis of HCC, clinical diagnosis, treatment and prognosis.

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“…Therefore, Lycorine is a potent direct inhibitor of CDK1, which can be utilized for the treatment of HCC [81]. Dihydroartemisinin (DHA) derived from Artemisia annua Linn is another naturally occurring inhibitor of CDK1, which has been shown to inhibit the cyclin B1-CDK1 pathway and HCC cell proliferation [82].…”

Section: Cdk1mentioning

confidence: 99%

Therapeutic Potential of Mitotic Kinases’ Inhibitors in Cancers of the Gastrointestinal System

Javed

Malagraba

Yarmohammadi

et al. 2022

Future Pharmacology

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Mitosis entails mechanistic changes required for maintaining the genomic integrity in all dividing cells. The process is intricate and temporally and spatially regulated by the ordered series of activation and de-activation of protein kinases. The mitotic kinases ensure the stepwise progression of entry into mitosis after the G2 phase of the cell cycle, followed by prophase, pro-metaphase, metaphase, anaphase, telophase, and subsequently cytokinesis and birth of two daughter cells with equal segregation and distribution of the genome. The major mitotic kinases include cyclin-dependent kinase 1 (CDK1), Aurora A and B Kinases, and Polo-Like-Kinase 1 (PLK1), among others. Overexpression of some of these kinases has been reported in many cancers as the mitotic fidelity and genome integrity are interlinked and dependent on these regulators, the native irregularities in these factors can be targeted as therapeutic strategies for various cancers. Here, we report and summarize the recent updates on the literature describing the various mitotic inhibitors targeting kinases, which can be used as potential therapeutic interventions for gastrointestinal cancers including gastric cancer, liver cancer, pancreatic cancer and colorectal cancer.

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Anti‑malarial drug dihydroartemisinin downregulates the expression levels of CDK1 and CCNB1 in liver cancer

Cited by 21 publications

References 37 publications

Dihydroartemisinin broke immune evasion through YAP1/JAK1/STAT1, 3 pathways to enhance anti-PD-1 therapy in hepatocellular carcinoma

Dihydroartemisinin broke immune evasion through YAP1/JAK1/STAT1, 3 pathways to enhance anti-PD-1 therapy in hepatocellular carcinoma

Identification and validation of real hub genes in hepatocellular carcinoma based on weighted gene co-expression network analysis

Therapeutic Potential of Mitotic Kinases’ Inhibitors in Cancers of the Gastrointestinal System

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