MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma

Yang, Mengkai; Zhang, Tao; Zhang, Yangfeng; Ma, Xiao‐Jun; Han, Jing; Zeng, Ke; Jiang, Yafei; Wang, Zongyi; Wang, Zhuoying; Xu, Jing; Hua, Yingqi; Cai, Zhengdong; Sun, Wei

doi:10.1186/s13046-021-01965-z

Cited by 8 publications

(8 citation statements)

References 45 publications

(48 reference statements)

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“…MYLK4 encodes a member of the myosin light chain kinase (MYLK) family. MYLKs are involved in the phosphorylation of the myosin light chain and promote the contraction of smooth muscle cells leading to bronchoconstriction [ 34 ]. Although studies on MYLK4 are limited, MYLKs are known to participate in cell migration, invasion, and proliferation [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells

Perez-Garcia,

Pino-Yanes,

Plender

et al. 2023

Clin Epigenet

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Background Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables. Results We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children (n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p < 9 × 10–8). Albuterol predominantly induced a hypomethylation effect on CpGs captured by the EPIC array across the genome (probability of hypomethylation: 76%, p value = 3.3 × 10–5). DNAm changes on the CpGs cg23032799 (CREB3L1), cg00483640 (MYLK4-LINC01600), and cg05673431 (KSR1) were validated in nasal epithelia from 10 independent donors (false discovery rate [FDR] < 0.05). The effect on the CpG cg23032799 (CREB3L1) was cross-tissue validated in bronchial epithelial cells at nominal level (p = 0.030). DNAm changes in these three CpGs were shown to be influenced by three independent genetic variants (FDR < 0.05). In silico analyses showed these polymorphisms regulated gene expression of nearby genes in lungs and/or fibroblasts including KSR1 and LINC01600 (6.30 × 10–14 ≤ p ≤ 6.60 × 10–5). Additionally, hypomethylation at the CpGs cg10290200 (FLNC) and cg05673431 (KSR1) was associated with increased gene expression of the genes where they are located (FDR < 0.05). Furthermore, while the epigenetic effect of albuterol was independent of the asthma status, severity, and use of medication, BDR was nominally associated with the effect on the CpG cg23032799 (CREB3L1) (p = 0.004). Gene-set enrichment analyses revealed that epigenomic modifications of albuterol could participate in asthma-relevant processes (e.g., IL-2, TNF-α, and NF-κB signaling pathways). Finally, nine differentially methylated regions were associated with albuterol treatment, including CREB3L1, MYLK4, and KSR1 (adjusted p value < 0.05). Conclusions This study revealed evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma.

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Section: Discussionmentioning

confidence: 99%

Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells

Perez-Garcia,

Pino-Yanes,

Plender

et al. 2023

Clin Epigenet

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“…[30] The relationship between osteosarcoma and MYLK is also being unveiled. Yang et al [31] demonstrated through mass spectrometry analysis that MYLK4 interacts with the epidermal growth factor receptor in osteosarcoma cells, promoting growth and metastasis through the epidermal growth factor receptor signaling pathway. Overexpression of MYLK4 accelerates OS growth and metastasis, while silencing MYLK4 expression leads to reduced cell growth and migration.…”

Section: Discussionmentioning

confidence: 99%

Hub biomarkers in ultrasound-guided bladder cancer and osteosarcoma: Myosin light chain kinase and caldesmon

Li,

Lin,

Cui

et al. 2023

Medicine

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Bladder cancer and osteosarcoma are 2 types of cancers that originate from epithelial tissues inside the bladder and bone or muscle tissues. Ultrasound-guided biopsies provide crucial support for the diagnosis and treatment of bladder cancer and osteosarcoma. However, the relationship between myosin light chain kinase (MYLK) and caldesmon (CALD1) and bladder cancer and osteosarcoma remains unclear. The bladder cancer datasets GSE65635 and GSE100926, the osteosarcoma dataset GSE39058, were obtained from gene expression omnibus. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis was performed. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis. Gene expression heat map was drawn and immune infiltration analysis was performed. The comparative toxicogenomics database analysis were performed to find disease most related to core gene. Western blotting experiments were performed. TargetScan screened miRNAs that regulated central DEGs. We obtained 54 DEGs. Functional enrichment analysis revealed significant enrichment in terms of cellular differentiation, cartilage development, skeletal development, muscle actin cytoskeleton, actin filament, Rho GTPase binding, DNA binding, fibroblast binding, MAPK signaling pathway, apoptosis, and cancer pathways. Gene set enrichment analysis indicated that DEGs were primarily enriched in terms of skeletal development, cartilage development, muscle actin cytoskeleton, MAPK signaling pathway, and apoptosis. The immune infiltration analysis showed that when T cells regulatory were highly expressed, Eosinophils exhibited a similar high expression, suggesting a strong positive correlation between T cells regulatory and Eosinophils, which might influence the disease progression in osteosarcoma. We identified 6 core genes (SRF, CTSK, MYLK, VCAN, MEF2C, CALD1). MYLK and CALD1 were significantly correlated with survival rate and exhibited lower expression in bladder cancer and osteosarcoma samples compared to normal samples. Comparative toxicogenomics database analysis results indicated associations of core genes with osteosarcoma, bladder tumors, bladder diseases, tumors, inflammation, and necrosis. The results of Western blotting showed that the expression levels of MYLK and CALD1 in bladder cancer and osteosarcoma were lower than those in normal tissues. MYLK and CALD1 likely play a role in regulating muscle contraction and smooth muscle function in bladder cancer and osteosarcoma. The lower expression of MYLK and CALD1 is associated with poorer prognosis.

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“…236,237 Notably, gefitinib (Gef), an efficient EGFR inhibitor, can also repolarize the pulmonary macrophage phenotype by disturbing macrophage receptor-interacting protein kinase 2 (RIPK2) expression to suppress the invasion and metastasis of osteosarcoma. [238][239][240] Additionally, Gef can also relieve postoperation-accelerated osteosarcoma metastasis and prolong overall survival time in a mouse model of osteosarcoma. 241 Various compounds have also been derived from natural products, including epimedokoreanin B (derived from Epimedii Herba), 242 onion A1 (derived from allium sulfides), 243 and oleanolic acid (OA)/corosolic acid (CA).…”

Section: Conventional Immunotherapy For Osteosarcomamentioning

confidence: 99%

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Tian

Cao

et al. 2023

Bone Res

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Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding the efforts of researchers, its five-year survival rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis. Therefore, managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease. Additionally, given the advances in nanomedicine, there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics. Here, we review the classification, characteristics, and functions of the key components of the immune microenvironment in osteosarcoma. This review also emphasizes the application, progress, and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment. Furthermore, we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

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MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma

Cited by 8 publications

References 45 publications

Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells

Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells

Hub biomarkers in ultrasound-guided bladder cancer and osteosarcoma: Myosin light chain kinase and caldesmon

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

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