E6E7 regulates the HK2 expression in cervical cancer via GSK3β/FTO signal

Liu, Chunyan; Li, Yangyang; Dong, Changyan; Qu, Luyun; Zuo, Ying

doi:10.1016/j.abb.2022.109389

Cited by 11 publications

(7 citation statements)

References 41 publications

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“…[28] HK2 is a member of the HK family and is an enzyme that catalyzes the conversion of glucose to glucose-6-phosphate. [29] Previous studies have found that HK2 is highly expressed in cervical cancer and may play an oncogenic role in cervical cancer through the miR-9-5p/HK2/AKT pathway. [30] In the GO functional enrichment analysis, the major hub genes localized mainly to MAP kinase tyrosine serine/threonine phosphatase activity, epidermal growth factor receptor binding, translational repressor activity, mRNA regulatory element binding, and others, their functions were mainly associated with the cell proliferation, differentiation, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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The feasibility of using the compound kushen injection to treat cervical cancer based on network pharmacology and transcriptomics

Zhang,

Xu,

2023

Medicine

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Background: To investigate the molecular targets and mechanisms of compound kushen injection (CKI) in the prevention and treatment of cervical cancer based on network pharmacology and transcriptomics. Methods: In this study, we used network pharmacology methods to screen for effective compounds, integrated the results of network pharmacology and RNA-seq to comprehensively screen and predict target genes, analyze the biological functions and signaling pathways of target genes, and construct a PPI network to screen for hub genes. The results were further verified by biological experiments, molecular docking, RT-PCR, and western blot analysis. Results: The results showed that the hub genes CXCL2, anti-vascular endothelial growth factor, hexokinase 2 are therapeutic targets of CKI for the treatment of Cervical Cancer. These targets were significantly enriched in pathways mainly including pathways in cancer, cell cycle, MAPK signaling pathways, etc. In vitro cell experiments showed that CKI could effectively inhibit the proliferation of cancer cells, promote apoptosis, and induce cell cycle arrest. RT-PCR and western blot experiments showed that the expression of hub genes was significantly decreased. The compounds have good binding activity to hub genes. Conclusion: CKI, based on its active ingredients and through multiple targets and multiple pathways, can stop the growth of cervical cancer cells at a certain phase of the cell cycle and cause apoptosis, which proved CKI’s effect in treating cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The feasibility of using the compound kushen injection to treat cervical cancer based on network pharmacology and transcriptomics

Zhang,

Xu,

2023

Medicine

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“…Viral E6 and E7 oncogenes are required for malignant transformation of cells. 60 The growth of HPV-positive cancer cells depends on the sustained expression of the viral E6 and E7 oncogenes. 61 In addition, studies have shown that E7 can also activate AKT.…”

Section: Discussionmentioning

confidence: 99%

“…This supports the conclusion that E6 upregulates TKT activity and activates nonoxidative PPP. Viral E6 and E7 oncogenes are required for malignant transformation of cells 60 . The growth of HPV‐positive cancer cells depends on the sustained expression of the viral E6 and E7 oncogenes 61 .…”

Section: Discussionmentioning

confidence: 99%

Human papillomavirus type 16 E6 promotes cervical cancer proliferation by upregulating transketolase enzymatic activity through the activation of protein kinase B

Hao,

Meng,

Sun

et al. 2023

Molecular Carcinogenesis

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Over 99% of precancerous cervical lesions are associated with human papillomavirus (HPV) infection, with HPV types 16 and 18 (especially type 16) found in over 70% of cervical cancer cases globally. E6, a critical HPV gene, triggers malignant proliferation by degrading p53; however, this mechanism alone cannot fully explain the oncogenic effects of HPV16 E6. Therefore, we aimed to investigate new targets of HPV oncogenic mechanisms. Our results revealed significant changes in nonoxidative pentose phosphate pathway (PPP) metabolites in HPV16‐positive cells. However, the role of nonoxidative PPP in HPV‐associated cell transformation and tumor development remained unexplored. In this study, we investigated the impact and mechanisms of HPV16 E6 on cervical cancer proliferation using the HPV‐negative cervical cancer cell line (C33A). HPV16 E6 was found to promote cervical cancer cell proliferation both in vitro and in vivo, activating the nonoxidative PPP. Transketolase (TKT), a key enzyme in the nonoxidative PPP, is highly expressed in cervical cancer tissues and associated with poor prognosis. HPV16 E6 promotes cervical cancer cell proliferation by upregulating TKT activity through the activation of AKT. In addition, oxythiamine (OT), a TKT inhibitor, hindered tumor growth, with enhanced effects when combined with cisplatin (DDP). In conclusion, HPV16 E6 promotes cervical cancer proliferation by upregulating TKT activity through the activation of AKT. OT demonstrates the potential to inhibit HPV16‐positive cervical cancer growth, and when combined with DDP, could further enhance the tumor‐suppressive effect of DDP.

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“…Functional analysis has shown that METTL3 pronounces the Warburg effect in CC cells by mobilizing YTHDF1 to stabilize HK2 expression 384 . The upregulated expression of human papillomavirus (HPV) E6/E7 drives aerobic glycolysis in CC by directing IGF2BP2 to actively regulate MYC methylation or upregulate serine/threonine kinase GSK‐3β expression and by degrading m 6 A demethylase FTO to increase HK2 expression 385,386 . In renal cell carcinoma (RCC), METTL14 downregulates the expression of bromodomain PHD finger transcription factor (BPTF) to attenuate the oncogenic transcriptome, glycolytic reprogramming, and distal lung metastasis 387 .…”

Section: Rna Methylation and Cancer Metabolismmentioning

confidence: 99%

Critical roles and clinical perspectives of RNA methylation in cancer

Li,

Yao,

Liu

et al. 2024

MedComm

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RNA modification, especially RNA methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all RNA modifications. It plays a significant role in RNA metabolism, affecting RNA processing, stability, and translation, thereby modulating gene expression and cell functions essential for proliferation, survival, and metastasis. Increasing studies have revealed the disruption in RNA metabolism mediated by RNA methylation has been implicated in various aspects of cancer progression, particularly in metabolic reprogramming and immunity. This disruption of RNA methylation has profound implications for tumor growth, metastasis, and therapy response. Herein, we elucidate the fundamental characteristics of RNA methylation and their impact on RNA metabolism and gene expression. We highlight the intricate relationship between RNA methylation, cancer metabolic reprogramming, and immunity, using the well‐characterized phenomenon of cancer metabolic reprogramming as a framework to discuss RNA methylation's specific roles and mechanisms in cancer progression. Furthermore, we explore the potential of targeting RNA methylation regulators as a novel approach for cancer therapy. By underscoring the complex mechanisms by which RNA methylation contributes to cancer progression, this review provides a foundation for developing new prognostic markers and therapeutic strategies aimed at modulating RNA methylation in cancer treatment.

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E6E7 regulates the HK2 expression in cervical cancer via GSK3β/FTO signal

Cited by 11 publications

References 41 publications

The feasibility of using the compound kushen injection to treat cervical cancer based on network pharmacology and transcriptomics

The feasibility of using the compound kushen injection to treat cervical cancer based on network pharmacology and transcriptomics

Human papillomavirus type 16 E6 promotes cervical cancer proliferation by upregulating transketolase enzymatic activity through the activation of protein kinase B

Critical roles and clinical perspectives of RNA methylation in cancer

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