&lt;p&gt;LHX6 Affects Erlotinib Resistance and Migration of &lt;em&gt;EGFR&lt;/em&gt;-Mutant Non-Small-Cell Lung Cancer HCC827 Cells Through Suppressing Wnt/β-Catenin Signaling&lt;/p&gt;

Wang, Qiang; Liu, Jinrong; Zhou, He; Su, Ying; Dong, Lin; Xu, Ling; Xu, Haipeng; Lin, Jinghui

doi:10.2147/ott.s258896

Cited by 16 publications

(7 citation statements)

References 46 publications

(66 reference statements)

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“…UCHL1 is also associated with many types of cancers including lung, colorectal, breast cancer, and pancreatic, which can promote tumor progression [ 62 , 63 ]. LHX6 is associated with many kinds of cancers and can inhibit the proliferation, invasion, and migration of breast cancer cells by modulating the PI3K/Akt/mTOR and Wnt/β-catenin signaling pathways [ 64 , 65 , 66 ]. LHX6 plays a tumor-suppressing role in MC-LR-induced liver cancer through the Wnt/β-catenin and P53 pathways [ 67 ].…”

Section: Resultsmentioning

confidence: 99%

A Novel 16-Genes Signature Scoring System as Prognostic Model to Evaluate Survival Risk in Patients with Glioblastoma

2022

Biomedicines

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Previous studies have found that gene expression levels are associated with prognosis and some genes can be used to predict the survival risk of glioblastoma (GBM) patients. However, most of them just built the survival-related gene signature, and personal survival risk can be evaluated only in group. This study aimed to find the prognostic survival related genes of GBM, and construct survival risk prediction model, which can be used to evaluate survival risk by individual. We collected gene expression data and clinical information from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Cox regression analysis and LASSO-cox regression analysis were performed to get survival-related genes and establish the overall survival prediction model. The ROC curve and Kaplan Meier analysis were used to evaluate the prediction ability of the model in training set and two independent cohorts. We also analyzed the biological functions of survival-related genes by GO and KEGG enrichment analysis. We identified 99 genes associated with overall survival and selected 16 genes (IGFBP2, GPRASP1, C1R, CHRM3, CLSTN2, NELL1, SEZ6L2, NMB, ICAM5, HPCAL4, SNAP91, PCSK1N, PGBD5, INA, UCHL1 and LHX6) to establish the survival risk prediction model. Multivariate Cox regression analysis indicted that the risk score could predict overall survival independent of age and gender. ROC analyses showed that our model was more robust than four existing signatures. The sixteen genes can also be potential transcriptional biomarkers and the model can assist doctors on clinical decision-making and personalized treatment of GBM patients.

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Section: Resultsmentioning

confidence: 99%

A Novel 16-Genes Signature Scoring System as Prognostic Model to Evaluate Survival Risk in Patients with Glioblastoma

2022

Biomedicines

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“…In addition, the Wnt/β-catenin pathway mainly regulates important cellular functions such as cell proliferation, differentiation and apoptosis, and is involved in tumorigenesis and drug resistance of NSCLC (Stewart, 2014). In erlotinib-resistant HCC827/ER cells, suppressing the activation of the Wnt/β-catenin signaling can inhibit erlotinib resistance and cell migration (Wang et al, 2020). At the same time, EGFR mutations lead to nuclear accumulation of β-catenin, Frontiers in Pharmacology frontiersin.org 13 which activates the conduction of the Wnt pathway.…”

Section: Discussionmentioning

confidence: 99%

Feiyiliu Mixture sensitizes EGFRDel19/T790M/C797S mutant non-small cell lung cancer to osimertinib by attenuating the PRC1/Wnt/EGFR pathway

et al. 2023

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Introduction: Osimertinib is a potent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, the emergence of acquired resistance due to the EGFR-Del19/T790M/C797S mutation limits the clinical application of osimertinib. Feiyiliu Mixture (FYLM), a clinical experience formula of Chinese medicine, was used to treat lung cancer with good clinical efficacy. In this study, we aimed to investigate the mechanism by which Feiyiliu Mixture delays osimertinib resistance in EGFR-mutant cell lines and EGFR-mutant cell tumor-bearing mice.Methods: The osimertinib-resistant cell models were established in mouse Lewis lung carcinoma (LLC) cells transfected with EGFR-Del19/T790M/C797S mutant lentivirus. In cell experiments, after 48 h of treatment with Feiyiliu Mixture-containing serum, MTT assay was used to detect the relative cell viability, and western blotting was used to detect EGFR protein phosphorylation expression. In animal experiments, C57BL/6J mice were subcutaneously injected with Lewis lung carcinoma cells stably expressing EGFR-Del19/T790M/C797S mutations to construct a xenograft model. After 2 weeks of Feiyiliu Mixture and/or osimertinib treatment, the expression of proliferation-related, apoptosis-related and PRC1/Wnt/EGFR pathway markers was detected by real-time qPCR, western blotting and immunohistochemistry.Results: The results showed that when combined with osimertinib, Feiyiliu Mixture synergistically reduces proliferation and increases apoptosis to improve drug resistance. In vitro, Feiyiliu Mixture-containing serum reduced the EGFR phosphorylation. In vivo, Feiyiliu Mixture downregulated the expression of cyclin B1 and Bcl-2 while upregulating the level of cleaved Caspase-3 protein, indicating that Feiyiliu Mixture promotes apoptosis. Furthermore, Feiyiliu Mixture reduced the expression of p-EGFR, p-Akt, PRC1 and Wnt pathway-related proteins such as β-catenin, c-Myc and c-Jun.Conclusion: The present study identified that Feiyiliu Mixture inhibited PRC1/Wnt/EGFR pathway activation, reduced proliferation, and promoted apoptosis, thereby increasing the sensitivity of EGFR-mutant non-small cell lung cancer to osimertinib. Our study provided a new idea for Chinese medicine to play a role in enhancing efficacy and reducing toxicity in the treatment of non-small cell lung cancer.

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“… 16 , 30 , 31 , 32 LHX6 is downregulated in various cancers and inhibits cell proliferation, invasion, and migration. 23 , 24 , 26 , 33 , 34 However, the expression patterns of different LHX6 isoforms in cervical cancer are unknown. In the current study, we found that two LHX6 isoform groups were elevated in CC samples compared to NC tissue samples, whereas the LHX6 EX(+12) group was observed in both NC and CC, with the positive rate of 95.24% in NC and 98.31% in CC.…”

Section: Discussionmentioning

confidence: 99%

The exon 12‐containing LHX6 isoforms promote cervical cancer cell proliferation by regulating the MAPK signaling pathway

et al. 2022

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<p>LHX6 Affects Erlotinib Resistance and Migration of <em>EGFR</em>-Mutant Non-Small-Cell Lung Cancer HCC827 Cells Through Suppressing Wnt/β-Catenin Signaling</p>

Cited by 16 publications

References 46 publications

A Novel 16-Genes Signature Scoring System as Prognostic Model to Evaluate Survival Risk in Patients with Glioblastoma

A Novel 16-Genes Signature Scoring System as Prognostic Model to Evaluate Survival Risk in Patients with Glioblastoma

Feiyiliu Mixture sensitizes EGFRDel19/T790M/C797S mutant non-small cell lung cancer to osimertinib by attenuating the PRC1/Wnt/EGFR pathway

The exon 12‐containing LHX6 isoforms promote cervical cancer cell proliferation by regulating the MAPK signaling pathway

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