Tenascin C Promotes Glioma Cell Malignant Behavior and Inhibits Chemosensitivity to Paclitaxel via Activation of the PI3K/AKT Signaling Pathway

Zhang, Qingping; Xu, Binchu; Hu, Fulan; Chen, Xianjin; Liu, Xinmin; Zuo, Yuan

doi:10.1007/s12031-021-01832-8

Cited by 16 publications

(12 citation statements)

References 27 publications

(33 reference statements)

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“…The results showed that the depletion of TNC expression significantly attenuated the proliferation and migration abilities of the NSCLC cell lines. It has been found that the function of TNC is linked to the activation of the AKT signaling pathway, 37,38 we also found a reduction in the pAKT-Ser473 signal in the TNC-depleted cells. If TNC was the major downstream effector of EN2, we would be able to observe the similar phenomenon in EN2-PC9 and EN2-A549 cells.…”

Section: The Tnc-akt Axis Has a Critical Role In En2mediated Oncogeni...supporting

confidence: 71%

Engrailed 2 serves as a master regulator of the super‐enhancer in the TNC gene locus in non‐small cell lung cancer

Li,

Jiang,

Wang

et al. 2023

Environmental Toxicology

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Engrailed 2 (EN2) is a homeodomain‐containing protein that is dysregulated in many types of cancer. However, the role of EN2 in non‐small cell lung cancer (NSCLC) and the mechanism underlying its biological function are largely unclear. Here, we showed that EN2 played an oncogenic function in NSCLC and greatly enhanced the malignant phenotype of NSCLC cells. Meanwhile, EN2 was able to boost the expression of a well‐studied oncogenic Tenascin‐C (TNC) gene, which in turn activated the AKT signaling pathway. Interestingly, we found that EN2 directly bound to the super‐enhancer (SE) region in the TNC locus. The histone marker H3K27ac was also enriched in the region, indicating the activation of the SE. Treatment of the cells with JQ1, an inhibitor of SE activity, abrogated the effect of EN2 on the expression of TNC and phosphorylation of AKT‐Ser473. Collectively, our work unveils a novel mode of EN2 function, in which EN2 governs the SE in the TNC locus, consequently activating the oncogenic TNC–AKT axis in NSCLC.

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Section: The Tnc-akt Axis Has a Critical Role In En2mediated Oncogeni...supporting

confidence: 71%

Engrailed 2 serves as a master regulator of the super‐enhancer in the TNC gene locus in non‐small cell lung cancer

Li,

Jiang,

Wang

et al. 2023

Environmental Toxicology

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“…Globally, well known for the high probability of metastasis and recurrence, glioma is still a leading cause of mortality in brain tumors [ 20 ]. Despite advances in the diagnosis of glioma, most glioma patients can only be diagnosed at the intermediate and advanced stages when surgical resection is not an optimal option [ 21 ]. Therefore, accurate patient stratification based on reliable prognostic factors is essential for the decision of clinical management and the determination of a subset of glioma patients suitable for personalized treatment.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Gene Signature Based on Kinesin Family Members to Predict Prognosis in Glioma

Pan

Fang

2023

Medicina

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Background and Objectives: Extensive research indicates that the kinesin superfamily (KIFs) regulates tumor progression. Nonetheless, the potential prognostic and therapeutic role of KIFs in glioma has been limited. Materials and Methods: Four independent cohorts from The Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas (CGGA) database were generated into a large combination cohort for identification of the prognostic signature. Following that, systematic analyses of multi-omics data were performed to determine the differences between the two groups. In addition, IDH1 was selected for the differential expression analysis. Results: The signature consists of five KIFs (KIF4A, KIF26A, KIF1A, KIF13A, and KIF13B) that were successfully identified. Receiver operating characteristic (ROC) curves indicated the signature had a suitable performance in prognosis prediction with the promising predictive area under the ROC curve (AUC) values. We then explored the genomic features differences, including immune features and tumor mutation status between high- and low-risk groups, from which we found that patients in the high-risk group had a higher level of immune checkpoint modules, and IDH1 was identified mutated more frequently in the low-risk group. Results of gene set enrichment analysis (GSEA) analysis showed that the E2F target, mitotic spindle, EMT, G2M checkpoint, and TNFa signaling were significantly activated in high-risk patients, partially explaining the differential prognosis between the two groups. Moreover, we also verified the five signature genes in the Human Protein Atlas (HPA) database. Conclusion: According to this study, we were able to classify glioma patients based on KIFs in a novel way. More importantly, the discovered KIFs-based signature and related characteristics may serve as a candidate for stratification indicators in the future for gliomas.

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“…Globally, well known for the high probability of metastasis and recurrence, glioma is still a leading cause of mortality in brain tumors 20 . Despite advances in diagnosis of glioma, most glioma patients can only be diagnosed at the intermediate and advanced stage when surgical resection is not an optimal option 21 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensively analysis exploring the role of kinesin family members in glioma

Pan

Fang

2022

Preprint

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Background Extensive research indicates that kinesin superfamily (KIFs) regulates tumor progression. Nonetheless, there is little share of literature focused on the potential prognostic and therapeutic role of KIFs in glioma. Methods Four independent cohorts were generated into a large combination cohort. Data from The Cancer Genome Atlas (TCGA) database served as the training cohort and data from Chinese Glioma Genome Atlas (CGGA) database served as the validation cohort. The R software were used for statistical analysisa, FigureYa and the online tool of Xiantao were used for mapping. Results The signature consist of five KIFs (KIF4A, KIF26A, KIF1A, KIF13A and KIF13B) was successfully identified and showed good performance in prognosis prediction with AUC values corresponding for 1-, 3‐, and 5-years were 0.66, 0.78 and 0.75 in training cohort, and 0.77, 0.82 and 0.83 in validation cohort. We then explored the genomic features differences including immune features and tumor mutation status between high and low risk groups, from which we found that patients in high risk group had a higher level of immune checkpoint modules and IDH1 was identified mutated more frequently in low risk group. Results of GSEA analysis showed that E2F target, mitotic spindle, EMT, G2M checkpoint and TNFa signaling were significantly activated in high risk patients, partially explaining the differential prognosis between two groups. Besides, we also verified the five signature genes in the Human Protein Atlas (HPA) database, which identified of candidates for relevant biomarkers. Conclusion The KIFs based signature is a reliable biomarker for the prediction the prognosis of glioma. Glioma patients between two risk groups showed significant discrepancy in immune features, tumor mutation status and prognosis chcracteristics.

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Tenascin C Promotes Glioma Cell Malignant Behavior and Inhibits Chemosensitivity to Paclitaxel via Activation of the PI3K/AKT Signaling Pathway

Cited by 16 publications

References 27 publications

Engrailed 2 serves as a master regulator of the super‐enhancer in the TNC gene locus in non‐small cell lung cancer

Engrailed 2 serves as a master regulator of the super‐enhancer in the TNC gene locus in non‐small cell lung cancer

Identification of a Novel Gene Signature Based on Kinesin Family Members to Predict Prognosis in Glioma

Comprehensively analysis exploring the role of kinesin family members in glioma

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