The Study On The Machnism Of IGF2BP3 Modification Regulating SMC1A In Gastric Adenocarcinoma

Objective: Gastric cancer(GC)is one of the most common cancers globally,and nearly 45% of gastric cancer patients worldwide originate from China.N6-methyladenosine(m6A)is the most common and abundant epigenetic modification of eukaryotic mRNA.Insulin-like growth factor 2 binding protein 3(IGF2BP3),as an m6 A recognition protein,is mainly responsible for regulating mRNA post-transcriptional modification and regulates the stability localization translation of mRNA.Chromosomal structure maintenance protein 1A(SMC1A)belongs to the SMC protein family.It is highly expressed in various malignant tumors,including gastric cancer,colorectal cancer,prostate cancer,acute myeloid hematological tumors,and so on.SMC1 A can promote early tumor formation and tumorigenesis,promoting the invasion and metastasis of cancer cells.Using the TCGA database,it was found that the expression of SMC1 A in gastric cancer tissues had a higher level.However,its role in gastric cancer remains unclear.This study explored the potential role and mechanism of SMC1 A in gastric cancer.Methods:1.To analyze the difference between SMC1 A gene expression in gastric adenocarcinoma tissue and adjacent normal tissue in The Tumor Genome Atlas(TCGA)database.2.In the next step,through the query of the m6 AVar database,it was found that the SMC1 A gene had a site that could be methylated,and IGF2BP3 may recognize its site.RT-qPCR and Western blotting were used to detect the expression levels of SMC1 A in gastric cancer tissues and cell lines.3.A human gastric cancer cell model with knockdown or overexpression of the SMC1 A gene was established,and the effects of SMC1 A on the proliferation,invasion,and migration of gastric cancer cells were detected by CCK8,clone formation,Transwell invasion,and cell scratch assays,respectively.4.Methylated RNA co-immunoprecipitation qPCR method(Me RIP-qPCR)was used to detect the regulatory effect of IGF2BP3 on SMC1 A m6A level and the m6 A level of SMC1 A RNA.5.The RNA stability was detected by actinomycin D treatment,and the biological function of SMC1 A in the occurrence and development of gastric cancer through IGF2BP3-mediated m6 A modification was further studied.6.Student’s t-test carried out statistical analysis of research data.Results:1.The mRNA of SMC1 A is highly expressed in gastric cancer tissues.2.The mRNA and protein levels of SMC1 A were highly expressed in gastric cancer cell lines.3.Overexpression of SMC1 A can significantly enhance the proliferation,invasion,and migration of gastric cancer cells,while knockdown of SMC1 A can attenuate the proliferation,migration,and invasion of gastric cancer cells.4.Knockout of IGF2BP3 significantly reduced the stability of SMC1 A mRNA,decreased the expression of SMC1 A,and reduced the level of SMC1 A gene-specific m6 A methylation modification;and attenuated the induction of enhanced AGS gastric cancer cells by overexpression of SMC1 A.Proliferation,migration,and invasion capacity.Conclusions:1.SMC1 A plays an essential role in preventing and developing gastric cancer.SMC1 A positively regulates gastric cancer cells’ proliferation,invasion,and migration.2.SMC1 A can promote the proliferation,invasion,and migration of gastric cancer cells through IGF2BP3-mediated m6 A modification.