Connexins in Lung Cancer and Brain Metastasis

Luo, Kongjia; Chen, Changxu; Yang, Jiapeng; Huang, Yunchao; Cárdenas, Eduardo; Jiang, Jean X.

doi:10.3389/fonc.2020.599383

Cited by 5 publications

(3 citation statements)

References 74 publications

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“…The transmembrane proteins, connexins, form the gap junctions. Cxs can serve as tumor suppressors or tumor promoters depending on the stage and type of cancer ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

“…The transmembrane proteins, connexins, form the gap junctions. Cxs can serve as tumor suppressors or tumor promoters depending on the stage and type of cancer (52). DOCK4 belongs to the DOCK180 family, which has diverse cellspecific functions and plays an important role in the metastasis of various tumors such as breast cancer, melanoma, and glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

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Identification and validation of differentially expressed genes for targeted therapy in NSCLC using integrated bioinformatics analysis

Altaf

Ilyas

et al. 2023

Front. Oncol.

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BackgroundDespite the high prevalence of lung cancer, with a five-year survival rate of only 23%, the underlying molecular mechanisms of non-small cell lung cancer (NSCLC) remain unknown. There is a great need to identify reliable candidate biomarker genes for early diagnosis and targeted therapeutic strategies to prevent cancer progression.MethodsIn this study, four datasets obtained from the Gene Expression Omnibus were evaluated for NSCLC- associated differentially expressed genes (DEGs) using bioinformatics analysis. About 10 common significant DEGs were shortlisted based on their p-value and FDR (DOCK4, ID2, SASH1, NPR1, GJA4, TBX2, CD24, HBEGF, GATA3, and DDR1). The expression of significant genes was validated using experimental data obtained from TCGA and the Human Protein Atlas database. The human proteomic data for post- translational modifications was used to interpret the mutations in these genes.ResultsValidation of DEGs revealed a significant difference in the expression of hub genes in normal and tumor tissues. Mutation analysis revealed 22.69%, 48.95%, and 47.21% sequence predicted disordered regions of DOCK4, GJA4, and HBEGF, respectively. The gene-gene and drug-gene network analysis revealed important interactions between genes and chemicals suggesting they could act as probable drug targets. The system-level network showed important interactions between these genes, and the drug interaction network showed that these genes are affected by several types of chemicals that could serve as potential drug targets.ConclusionsThe study demonstrates the importance of systemic genetics in identifying potential drug- targeted therapies for NSCLC. The integrative system- level approach should contribute to a better understanding of disease etiology and may accelerate drug discovery for many cancer types.

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“…The transmembrane proteins, connexins, form the gap junctions. Cxs can serve as tumor suppressors or tumor promoters depending on the stage and type of cancer ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification and validation of differentially expressed genes for targeted therapy in NSCLC using integrated bioinformatics analysis

Altaf

Ilyas

et al. 2023

Front. Oncol.

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“…At present, the mechanism of brain metastasis includes metastasis cascade and tumor stem cell hypothesis [ 4 ], seed soil theory [ 5 ], gene driven theory [ 6 ], brain microenvironment influence, etc. [ 7 ], but the specific mechanism is still unclear, and the difficulty of establishing lung cancer brain metastasis model makes it difficult to carry out brain metastasis research, and many studies are still in the exploratory stage.The blood–brain barrier plays an important role in the process of brain metastasis.…”

Section: Introductionmentioning

confidence: 99%

EZH2 G553C significantly increases the risk of brain metastasis from lung cancer due to salt bridge instability

Wang,

Zhang

et al. 2024

Cancer Cell Int

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Background The incidence and mortality of lung cancer is the highest in China and the world. Brain is the most common distant metastasis site of lung cancer. Its transfer mechanism and predictive biomarkers are still unclear. EZH2 participates in the catalysis of transcriptional inhibition complex, mediates chromatin compactness, leads to the silencing of its downstream target genes, participates in the silencing of multiple tumor suppressor genes, and is related to cell proliferation, apoptosis and cycle regulation. In physiology, EZH2 has high activity in stem cells or progenitor cells, inhibits genes related to cell cycle arrest and promotes self-renewal. To detect the expression and mutation of EZH2 gene in patients with brain metastasis of lung cancer, and provide further theoretical basis for exploring the pathogenesis of brain metastasis of lung cancer and finding reliable biomarkers to predict brain metastasis of lung cancer. Methods This study investigated susceptible genes for brain metastasis of lung cancer. The second-generation sequencing technology was applied to screen the differential genes of paired samples (brain metastasis tissues, lung cancer tissues and adjacent tissues) of lung cancer patients with brain metastasi. Results It revealed that there was a significant difference in the G553C genotype of EZH2 between lung cancer brain metastasis tissues and lung cancer tissues (p = 0.045). The risk of lung cancer brain metastasis in G allele carriers was 2.124 times higher than that in C allele carriers. Immunohistochemistry showed that compared with lung cancer patients and lung cancer patients with brain metastasis, the expression level of EZH2 in lung cancer tissues of lung cancer patients was significantly higher than that in adjacent lung tissues (p < 0.0001), and higher than that in brain metastasis tissues (p = 0.0309). RNA in situ immunohybridization showed that EZH2 mRNA expression was gradually high in lung cancer adjacent tissues, lung cancer tissues and lung cancer brain metastasis tissues. Conclusions EZH2 G553C polymorphism contributes to the prediction of brain metastasis of lung cancer, in which G allele carriers are more prone to brain metastasis.

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