The Molecular Mechanism Of FAM136A Regulating The Progression Of Stomach Carcinoma

ObjectiveGastric cancer is one of the most common malignant tumors of the digestive system in humans,and its mortality rate ranks fourth among common malignant tumors.In-depth research on the mechanism of gastric cancer and the search for key target molecules will contribute to the early diagnosis and treatment of gastric cancer.FAM136A（Family with sequence similarity 136,member A gene）is expressed in a variety of cancer tissues and may regulate tumor progression,but its molecular mechanism remains unclear.Its expression in gastric cancer tissues and its role in regulating gastric cancer progression are currently There are no reports yet and further research is needed.This project aims to study the regulatory role of FAM136A in the progression of gastric cancer,clarify its specific mechanism,and make it a new target for clinical screening and treatment of gastric cancer.MethodsThe expression characteristics and clinicopathological significance of FAM136A in gastric cancer tissues were analyzed by immunohistochemical staining technique.The gastric cancer cell lines HGC-27 and AGS were transfected with FAM136A plasmid or si RNA to differentially express FAM136A,respectively.The regulatory effect of FAM136A on the migration,invasion and proliferation of gastric cancer cells was detected by Cell scratch assay,Transwell assay and MTT assay,respectively.The expression and activation of related target molecules and MAPK signaling pathway were detected by Western blot screening,and the molecular mechanism of their effects was clarified.ResultsWe collected 90 cases of gastric adenocarcinoma tissues,and found that FAM136A is highly expressed in gastric cancer tissues by immunohistochemical staining,mainly located in the cytoplasm,and its expression intensity varies with the pathological grade,T stage,and N stage differenently.After overexpression of FAM136A in HGC-27 and AGS cell lines,the Cell scratch assay and Transwell assay found that tumor cell migrative and invasive ability were enhanced,while down-regulation of FAM136A expression level in the two cell lines yielded opposite experimental results,suggesting that FAM136A can enhance gastric cancer cell migrative and invasive ability.The Western blot assay showed that after upregulating the expression level of FAM136A protein in gastric cancer cells,the protein expression levels of EMT（Epithelial-to-mesenchymal transition）related proteins Ecadherin and Claudin-1 decreased,while the protein expression level of N-cadherin,Snail,Slug and MMP2 was increased.Contrary experimental results were obtained after down-regulation of FAM136A expression levels in both cell lines.This suggests that FAM136A can promote gastric cancer cell migration and invasion by regulating EMT process.The MTT experiment found that after overexpression of FAM136A in HGC-27 and AGS cells,the cell proliferation ability was significantly improved,while the downregulation of FAM136A protein expression level inhibited the cell proliferation ability.The Western blot assay showed that the expression levels of cyclin D1,cyclin B1,and p-Rb increased after FAM136A was overexpressed in HGC-27 and AGS cell lines.Contrary experimental results were obtained after down-regulation of FAM136A protein expression levels in the two cell lines.The Western blot assay showed that the phosphorylation levels of MAPK（mitogen-activated protein kinase）pathway-related proteins ERK（extracellular regulated protein kinases）and JNK（c-Jun N-terminal kinase）changed synchronously with the increase and decrease of FAM136A protein expression.However,the expression and activation levels of AKT and other proteins did not change significantly,suggesting that FAM136A may regulate gastric cancer cell cycle and EMT through the MAPK/ERK and MAPK/JNK signaling pathways,thereby regulating the progression of gastric cancer.Conclusions1.FAM136A is highly expressed in gastric cancer tissues,mainly located in the cytoplasm,and its expression intensity varies with the pathological grade,T stage,and N stage.2.FAM136A enhances gastric cancer cell migration and invasion by regulating EMT.3.FAM136A can promote the proliferation of gastric cancer by regulating the cell cycle.4.FAM136A can regulate the activation level of ERK,JNK signaling pathway.However,the relationship with the aforementioned regulation of cell invasion,metastasis and proliferation needs to be further verified.