Imatinib inhibits the malignancy of hepatocellular carcinoma by suppressing autophagy

Xiao, Meng-Chao; Qian, Hui; Huang, Chia-Chi Flora; Zheng, Bai-Nan; Yan, Fang-Zhi; Liu, Fang; Zhang, Xin; Chen, Shijie; Luo, Cheng; Xie, Wei-Fen

doi:10.1016/j.ejphar.2021.174217

Cited by 11 publications

(5 citation statements)

References 42 publications

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“…Studies have shown that dual immune checkpoint blockade can enhance anti-tumor immunity to HCC( Du et al, 2021 ). For example, Imatinib reversed Sorafenib induced autophagy, and the combination of Imatinib and Sorafenib had a synergistic effect on HCC cells compared to monotherapy ( Xiao et al, 2021 ). Meanwhile, m6A methyltransferase METTL3 also enhanced Sorafenib’s ability to inhibit HCC by decreasing the autophagy pathway ( Lin et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

Tian

Nie

et al. 2022

Front. Mol. Biosci.

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Background: BTBD10 serves as an activator of Akt family members through decreasing the protein phosphatase 2A-mediated dephosphorylation. The present study attempted to investigate the prognostic value of BTBD10 in hepatocellular carcinoma (HCC), specially, its relationship with tumor-infiltrating lymphocytes (TILs).Methods: BTBD10 expression was evaluated in HCC using The Cancer Genome Atlas (TCGA) and Xijing Hospital database, and verified in HCC cell lines. Cox analyses were performed to analyze independent prognostic risk factors for HCC. The optimal cut-off value of BTBD10 was calculated, by which all patients were divided into two groups to compare the overall survival (OS). The signaling pathways were predicted, by which BTBD10 may affect the progression of HCC. To investigate the impact of BTBD10 on HCC immunotherapy, correlations between BTBD10 and TILs, immune checkpoints, m6A methylation-related genes and ferroptosis-related genes were assessed. The distribution of half-maximal inhibitory concentration (IC50) of diverse targeted drugs was observed based on the differential expression of BTBD10.Results: BTBD10 expression was higher in HCC tissues and cell lines than that of normal liver tissues and cells. The patients with high expression of BTBD10 showed a worse OS, as compared to that of BTBD10 low-expressing group. Cox analyses indicated that BTBD10 was an independent prognostic risk factor for HCC. Several molecular pathways of immune responses were activated in HCC patients with high-expressing of BTBD10. Furthermore, BTBD10 expression was demonstrated to be positively correlated with tumor-infiltrating B cells, T cells, macrophages, neutrophils and dendritic cells. Meanwhile, the expression of BTBD10 was synchronized with that of several m6A methylation-related genes, ferroptosis-related genes and immune checkpoints. The IC50 scores of Sorafenib, Navitoclax, Veliparib, Luminespib, and Imatinib were found to be lower in BTBD10 high-expressing HCC group.Conclusion: BTBD10 negatively regulates tumor immunity in HCC and exhibits adverse effect on the prognosis of HCC, which could be a potential target for immunotherapy.

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Section: Discussionmentioning

confidence: 99%

BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

Tian

Nie

et al. 2022

Front. Mol. Biosci.

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“…Imatinib prevents phosphorylation of protein kinase B (Akt) and promotes expression of p62 and suppresses progression of HCC in vitro and in vivo. Imatinib impairs HCC progression via regulating the above signaling pathways to inhibit autophagy [203].…”

Section: Synthetic Drugsmentioning

confidence: 99%

“…The most controversial part is that the function of autophagy in HCC is completely different depending on the conditions. For example, a previous experiment showed that imatinib suppresses autophagy in HCC therapy [203]. However, another experiment shows that ursodeoxycholic acid promotes LC3B expression to stimulate autophagy and thus prevent HCC progression [209].…”

Section: Natural Compoundsmentioning

confidence: 99%

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

et al. 2023

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Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy is observed in the development of human diseases, especially cancer. Autophagy has reciprocal functions in cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) is one of the most lethal and common malignancies of the liver, and smoking, infection, and alcohol consumption can lead to its development. Genetic mutations and alterations in molecular processes can exacerbate the progression of HCC. The function of autophagy in HCC is controversial and may be both tumor suppressive and tumor promoting. Activation of autophagy may affect apoptosis in HCC and is a regulator of proliferation and glucose metabolism. Induction of autophagy may promote tumor metastasis via induction of EMT. In addition, autophagy is a regulator of stem cell formation in HCC, and pro-survival autophagy leads to cancer cell resistance to chemotherapy and radiotherapy. Targeting autophagy impairs growth and metastasis in HCC and improves tumor cell response to therapy. Of note, a large number of signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs regulate autophagy in HCC. Moreover, regulation of autophagy (induction or inhibition) by antitumor agents could be suggested for effective treatment of HCC. In this paper, we comprehensively review the role and mechanisms of autophagy in HCC and discuss the potential benefit of targeting this process in the treatment of the cancer. Graphical abstract

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“…The current therapeutic drugs used in the treatment of HCC includes Lenvatinib, Sorafenib, Nivolumab, Cabozantinib, Atezolizumab, Bevacizumab, Imatinib, and others (Ikeda et al 2018; Tang et al 2020; Zhao et al 2020; Liu et al 2021; Xiao et al 2021). We obtained their target genes from the HCDT database (Table 2).…”

Section: Rusultsmentioning

confidence: 99%

Identification and functional analysis of eRNA markers for hepatocellular carcinoma based on high-throughput data

Chen,

Zhang

et al. 2023

Preprint

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Hepatocellular carcinoma (HCC) is a common type of liver cancer with a high mortality rate. enhancer RNA (eRNA) has been proved to play an important role in cancer progress and development. However, the eRNA studies in HCC are still limited. In this study, we attempted to identify some eRNA biomarkers for HCC diagnosis and analyzed their biological function. First, we identified three eRNA biomarkers (CAP2e, COLEC10e, and MARCOe), which were significant differentially expressed between tumor and normal tissues in 115 HCC patients across three datasets. CAP2e demonstrated upregulation in tumors while COLEC10e and MARCOe were downregulated. These results could be validated in TCGA-LIHC data. There were significant positive correlations between the expression of these eRNAs and their host genes. Then, functional enrichment analysis of protein-coding genes associated with the eRNA biomarkers revealed their involvement in cancer-related pathways. MARCOe was suggested to be a potential target for therapeutic drugs in HCC by a drug related study. The next, survival analysis demonstrated significant prognostic values of these eRNAs in prediction of overall survival. Immune infiltration analysis revealed a positive correlation between MARCOe expression and immune cell infiltration level. Finally, we found similar expression patterns of these eRNA biomarkers in other cancers, such as cholangiocarcinoma, through a pan-cancer comparison. CAP2e and COLEC10e in HCC were validated by other studies. However, the studies about MARCOe in HCC were limited. In conclusion, as best as our knowledge, it is the first time to identify three eRNA biomarkers for HCC diagnosis. These biomarkers are proved to be involved in HCC progress and development, have prognosis prediction values, and are potential to be therapeutic targets.

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Imatinib inhibits the malignancy of hepatocellular carcinoma by suppressing autophagy

Cited by 11 publications

References 42 publications

BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

Identification and functional analysis of eRNA markers for hepatocellular carcinoma based on high-throughput data

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