Targeting MYO1B/SNAI2/Cyclin D1 Axis Impairs The Esophageal Squamous Carcinoma

Objectives:To verify the mutation and abnormal expression of myolb in esophageal squamous cell carcinoma;To confirm whether myolb is involved in the biological process of proliferation,invasion,metastasis and drug resistance of esophageal squamous cell carcinoma;To predict the downstream genes and signal transduction pathways regulated by myolb,and clarify the related regulatory mechanisms;Objective to elucidate the clinical significance of myolb in esophageal squamous cell carcinoma(ESCC),and provide a potential therapeutic target for ESCC.Methods:1.TCGA,Oncomine,GEPIA public cancer databases were used to search the mRNA expression levels of target protein(MYO1B/SNAI2/CyclinD1)in esophageal cancer and normal tissues;David database was used to analyze the biological function enrichment of differentially expressed genes;2.The expression level of MYO1B was knocked down by RNAi gene silencing,and SNAI2 was overexpressed by viral vector;3.Real time fluorescent quantitative PCR was used to detect the mRNA expression level of the cells,WB was used to detect the cells,and immunohistochemistry was used to detect the protein expression level of the tissues;4.CCK8,colony formation assay and EdU fluorescence staining were used to detect the proliferation of esophageal cancer cells;5.Scratch healing test,chamber invasion and migration test were used to detect the metastasis and invasion ability of esophageal cancer cells;6.Excel、Graphpad Prism、Phoptoshop、Adobe Illustrator、SPSS software for data collection,collation,mapping and statistical analysis.Results:1.The results of database search showed that:1.6%of the samples had MYO1B MYO1B gene amplification at the gene level;the mRNA expression of MYO1B in esophageal cancer tissues was increased at the transcription level;the protein expression of MYO1B in clinical esophageal cancer tissues was increased at the translation level;2.Univariate analysis showed that high expression of MYO1B was associated with poor disease-free survival(DFS)and overall survival(OS);kaplan Meir survival analysis showed that patients with high expression of MYO1B had worse prognosis;Cox multivariate analysis showed that high expression of MYO1B was an independent risk factor for poor prognosis;3.The results of cell experiment showed that knockdown of MYO1B inhibited the proliferation,invasion and migration of esophageal cancer cells,increased the sensitivity of esophageal cancer cells to cisplatin;4.EMT is an activated signal pathway in esophageal cancer,and its core transcription factor SNAI2 is regulated by MYO1B.MYO1B participates in EMT signal transduction pathway by regulating SNAI2 gene,and then regulates the proliferation,invasion and migration of esophageal cancer cells;5.CyclinD1 is a downstream effector molecule of MYO1B/SNAI2 axis,which can be significantly inhibited by cell cycle inhibitor palbociclib;Conclusions:In this study,we found that the expression of MYO1B in esophageal squamous cell carcinoma was abnormal;MYO1B can regulate the proliferation,migration and invasion of ESCC through Snai2/cyclin D1.Knockdown of MYO1B can increase the sensitivity of ESCC to cisplatin;High expression of MYO1B is associated with short disease-free survival and overall survival,and is an independent risk factor for ESCC;MYO1B is a potential prognostic marker and a potential therapeutic target for esophageal squamous cell carcinoma;Targeting MYO1B in combination with cell cycle inhibitor palbociclib can enhance the ability to inhibit the proliferation,invasion and metastasis of esophageal squamous cell carcinoma cells,which can help to improve the future drug treatment of esophageal cancer.