MYBL1 induces transcriptional activation of ANGPT2 to promote tumor angiogenesis and confer sorafenib resistance in human hepatocellular carcinoma

Zhu, Jinrong; Wu, Yongqi; Yu, Yijian; Li, Yan; Shen, Jianfei; Zhang, Rongxin

doi:10.1038/s41419-022-05180-2

Cited by 22 publications

(13 citation statements)

References 42 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[20]. ANGPT2 was related to drug resistance and its high expression will increases sorafenib resistance [23]. ANGPT2 also promoted epithelial mesenchymal transition, and its expression level was negatively correlates with survival, making it a prognostic marker for HCC [24].…”

Section: Discussionmentioning

confidence: 99%

Identification of ANGPT2, FLT3, IGF1 and SPP1 related to glycolysis and PI3K/Akt signaling pathway in hepatocellular carcinoma

Zhang,

Xu,

Shi

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Hepatocellular carcinoma (HCC) is a malignant tumor of the liver. Aerobic glycolysis is the reason for the high proliferation rate of HCC cells. In addition, PI3K / Akt pathway stimulates angiogenesis, which is beneficial to the growth of HCC cells. The aim of this research was to screen biomarkers related to glycolysis and PI3K/Akt signaling pathway in HCC. Methods In TCGA-LIHC dataset, differential analysis was performed to screen out the DEGs between tumor and normal groups. The candidate genes were obtained through overlapping DEGs, GMRGs and PI3K/Akt signaling pathway-related genes. Biomarkers were identified by ten algorithms in the PPI network. The correlation between angiogenesis/autophagy/apoptosis/EMT and biomarkers was analyzed. Results A sum of 7476 DEGs were obtained between tumor and normal groups. Soon afterwards, 20 candidate genes were obtained. Then, we identified 4 biomarkers (ANGPT2, FLT3, IGF1 and SPP1) via PPI. we found these biomarkers were positively associated with angiogenesisa, autophagy, apoptosis and EMT. Finally, ANGPT2 and SPP1 was higher expressed in HCC group compared to the normal group. Conclusion Overall, we obtained four biomarkers related to glycolysis and PI3K/Akt signaling pathway (ANGPT2, FLT3, IGF1 and SPP1) associated with HCC, which laid a theoretical foundation for the treatment of HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of ANGPT2, FLT3, IGF1 and SPP1 related to glycolysis and PI3K/Akt signaling pathway in hepatocellular carcinoma

Zhang,

Xu,

Shi

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…ATO inhibits tumor growth and angiogenesis of HCC by blocking the paracrine signaling of Ang-1 and Ang-2 through the inhibition of the p-Akt/HIF-1α pathway after IRFA Angiogenesis is an essential process in the growth and metastasis of HCC (Zhu et al, 2022). Angiogenesis is not only regulated by VEGF but also by angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), and their receptor Tie-2 (Engin et al, 2012).…”

Section: Hif-1α/bnip3 Pathway Promotes Residual Hcc Cell Progression ...mentioning

confidence: 99%

“…Angiogenesis is an essential process in the growth and metastasis of HCC ( Zhu et al, 2022 ). Angiogenesis is not only regulated by VEGF but also by angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), and their receptor Tie-2 ( Engin et al, 2012 ).…”

Section: Ato Inhibits Tumor Growth and Angiogenesis Of Hcc By Blockin...mentioning

confidence: 99%

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

Xiao

Liu

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the most common digestive malignancies. HCC It ranges as the fifth most common cause of cancer mortality worldwide. While The prognosis of metastatic or advanced HCC is still quite poor. Recently, locoregional treatment, especially local ablation therapies, plays an important role in the treatment of HCC. Radiofrequency ablation (RFA) and high-intensity focused ultrasound (HIFU) ablation are the most common-used methods effective and feasible for treating HCC. However, the molecular mechanisms underlying the actions of ablation in the treatments for HCC and the HCC recurrence after ablation still are poorly understood. Hypoxia-inducible factor (HIF), the key gene switch for adaptive responses to hypoxia, has been found to play an essential role in the rapid aggressive recurrence of HCC after ablation treatment. In this review, we summarized the current evidence of the roles of HIF in the treatment of HCC with ablation. Fifteen relevant studies were included and further analyzed. Among them, three clinical studies suggested that HIF-1α might serve as a crucial role in the RAF treatment of HCC or the local recurrence of HCC after RFA. The remainder included experimental studies demonstrated that HIF-1, 2α might target the different molecules (e.g., BNIP3, CA-IX, and arginase-1) and signaling cascades (e.g., VEGFA/EphA2 pathway), constituting a complex network that promoted HCC invasion and metastasis after ablation. Currently, the inhibitors of HIF have been developed, providing important proof of targeting HIF for the prevention of HCC recurrence after IRFA and HIFU ablation. Further confirmation by prospective clinical and in-depth experimental studies is still warranted to illustrate the effects of HIF in HCC recurrence followed ablation treatment in the future.

show abstract

“…The MYBL1 has been implicated in multiple diseases. Zhu et al indicated that MYBL1 was tightly associated with higher endothelial vessel density by inducing the transcriptional activation of ANGPT2, further affecting sorafenib resistance in liver cancer (7). Guo et al indicated that the O-GlcNAc can regulate MYBL1 expression in an epigenetic modification manner, leading to an aberrant cancer stem cell compartment and cancer progression (8).…”

Section: Introductionmentioning

confidence: 99%

“…Zhu et al. indicated that MYBL1 was tightly associated with higher endothelial vessel density by inducing the transcriptional activation of ANGPT2, further affecting sorafenib resistance in liver cancer ( 7 ). Guo et al.…”

Section: Introductionmentioning

confidence: 99%

Integration analysis identifies MYBL1 as a novel immunotherapy biomarker affecting the immune microenvironment in clear cell renal cell carcinoma: Evidence based on machine learning and experiments

et al. 2022

View full text Add to dashboard Cite

BackgroundPrevious studies have identified MYBL1 as a cancer-promoting molecule in numerous types of cancer. Nevertheless, the role of MYBL in renal cancer remains unclear.MethodsGenomic and clinical data of clear cell renal cell carcinoma (ccRCC) was get from the Cancer Genome Atlas (TCGA) database. CCK8, colony formation, and 5-ethynyl-2’-deoxyuridine assay were utilized to evaluate the performance of cell proliferation. Cell apoptosis was detected using the flow cytometric analysis. The protein level of MYBL1 in different tissues was evaluated using immunohistochemistry. A machine learning algorithm was utilized to identify the prognosis signature based on MYBL1-derived molecules.ResultsHere, we comprehensively investigated the role of MYBL1 in ccRCC. Here, we noticed a higher level of MYBL1 in ccRCC patients in both RNA and protein levels. Further analysis showed that MYBL1 was correlated with progressive clinical characteristics and worse prognosis performance. Biological enrichment analysis showed that MYBL1 can activate multiple oncogenic pathways in ccRCC. Moreover, we found that MYBL1 can remodel the immune microenvironment of ccRCC and affect the immunotherapy response. In vitro and in vivo assays indicated that MYBL1 was upregulated in ccRCC cells and can promote cellular malignant behaviors of ccRCC. Ultimately, an machine learning algorithm – LASSO logistics regression was utilized to identify a prognosis signature based on the MYBL1-derived molecules, which showed satisfactory prediction ability on patient prognosis in both training and validation cohorts.ConclusionsOur result indicated that MYBL1 is a novel biomarker of ccRCC, which can remodel the tumor microenvironment, affect immunotherapy response and guide precision medicine in ccRCC.

show abstract

MYBL1 induces transcriptional activation of ANGPT2 to promote tumor angiogenesis and confer sorafenib resistance in human hepatocellular carcinoma

Cited by 22 publications

References 42 publications

Identification of ANGPT2, FLT3, IGF1 and SPP1 related to glycolysis and PI3K/Akt signaling pathway in hepatocellular carcinoma

Identification of ANGPT2, FLT3, IGF1 and SPP1 related to glycolysis and PI3K/Akt signaling pathway in hepatocellular carcinoma

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

Integration analysis identifies MYBL1 as a novel immunotherapy biomarker affecting the immune microenvironment in clear cell renal cell carcinoma: Evidence based on machine learning and experiments

Contact Info

Product

Resources

About