Relationship Between The Development Of TMED11P And Pancreatic Ductal Adenocarcinoma

The incidence of adenocarcinoma of the adenocarcinoma is concealed,the incidence rate is high,and the prognosis of clinical treatment is mostly poor in the diagnosis.The occurrence of pancreatic ductal adenocarcinoma is affected by many factors,which may be related to unhealthy lifestyle,gene mutation,memory silencing,uncontrolled gene expression,and cell signaling disorders.Although some indicators have been developed to diagnose or predict pancreatic ductal adenocarcinoma,the specificity and sensitivity are poor.Exploring and discovering some new biomarker molecules that predict the clinical prognosis of patients with pancreatic ductal adenocarcinoma can help to provide more important information for clinical treatment.Long-chain non-coding RNAs(IncRNAs)are transcribed by the genome and cannot translate RNA molecules longer than 200nt in length.With a lot of in-depth research,IncRNA has a certain understanding,it participates in the body’s physiological functions,regulation of gene expression,gene silencing or activation,chromatin modification,transcriptional activation or interference,nuclear transport and other important regulatory processes..Some studies have found that in different tumors,certain IncRNA expression levels may undergo fundamental changes in tumor tissue and normal tissue species,which may be used as tumor markers for diagnostic treatment or prognosis prediction..In addition,studies have shown that IncRNA may act as a tumor suppressor gene or affect tumor suppressor genes during tumor growth,reduce apoptosis and promote tumor proliferation.IncRNA has also been found to play an important role in tumor metastasis.Studies have shown that IncRNA is involved in the epigenetic regulation of protein-coding gene expression,and the elucidation of its mechanism will provide a new direction for cancer therapy.Studies have shown that IncRNA specifically expresses in pancreatic cancer.Some studies have shown that TMED11P is a highly conserved IncRNAs,which is involved to some extent in the pathogenesis of pancreatic ductal adenocarcinoma.This study firstly conducted a preliminary study on the function of TMED11P at the cellular level,and confirmed that the relative expression levels of TMED11P were different in PNAC-1,MIA PACA-2,AsPc-1,and BxPc-3 cells,among which MIA PACA The expression level of-2 was the highest and the expression level of AsPc-1 was the lowest.MIA PACA-2 cells and ASPC-1 cells were selected by transient transfection,and cells with up-regulated and down-regulated TMED11P gene expression were constructed.The expression level of TMED11P gene is inversely related to the level of cell proliferation.The expression level of TMED11P gene decreased,the cell proliferation level increased;the expression of TMED11P gene increased,and the cell proliferation level was inhibited;the down-regulation of TMED11P gene expression level and the up-regulation of TMED11P gene expression level were significantly different(P<0.05).Down-regulation of the TMED1 IP gene enhances the healing ability of MIA PACA-2 and ASPC-1 cells.An increase in TMED11P gene expression can impair the healing ability of MIA PACA-2 and ASPC-1 cells.Compared with the down-regulation of the cell-expressing ability of TMED11P gene,the cell healing ability of up-regulated TMED11P gene was significantly reduced.The invasive ability of MIA PACA-2 and ASPC-1 cells was significantly inhibited after up-regulation of TMED11P gene(P<0.05),while the invasive ability of TMED11P gene was significantly increased(P<0.05).In order to better confirm the function of TMED11P gene,MIA PACA-2 and ASPC-1 cells were used to construct a cell line stably up-regulating and down-regulating TMED11P gene,and TMED11P gene was further verified in animals to regulate MIA PACA-2 and ASPC-1 The proliferation of cells,and the relationship between the expression level of TMED11P gene and the therapeutic effect of gemcitabine.Two stable up-regulated expressions and two stable down-regulated expressions of TMED11P gene were successfully constructed,namely:ASPC-1/HiRNA,MIA PACA-2/HiRNA,ASPC-1/SiRNA,MIA PACA-2/SiRNA.It was confirmed again that the expression level of TMED11P gene was different on the stably transfected cell line,which affected the proliferation ability of pancreatic cancer cells.That is,the expression of TMED11P gene is up-regulated,and the proliferative ability of pancreatic cancer cells is inhibited.The expression of TMED11P gene is decreased,and the proliferative ability of pancreatic cancer cells is enhanced.The expression of TMED11P in pancreatic cancer cells increased,the IC50 decreased,the expression of TMED11P decreased,and the IC50 increased.After treatment with gemcitabine in vitro,the proportion of early apoptosis and the proportion of late apoptosis in pancreatic cancer cells with high expression of TMED11P increased compared with the control group(P<0.05);the proportion of early apoptosis of pancreatic cancer cells with low expression of TMED11P and late withering The proportion of death was reduced(P<0.05).The size of tumors formed by pancreatic cancer cells with different expression levels of TMED11P was different after vaccination in nude mice.The tumors n TMED11P high expression group were smaller,and the tumors in TMED11P low expression group were larger.Gemcitabine was used to study the proliferation of pancreatic cancer cells in different doses of TMED11P in nude mice.Compared with the control group,the cells inoculated with TMED11P high expression group had smaller tumors and better therapeutic effect;pancreatic cancer inoculated with TMED11P low expression group The cells form larger tumors and the treatment effect is poor.The effects of gemcitabine on the body weight,liver and kidney function and blood cells of nude mice were studied in nude mice.The results showed that the weight gain of TMED11P treatment group was significantly increased compared with the untreated group(p<0.05).Analysis and comparison of body weight data between the three groups of untreated groups showed that the low expression of TMED11P in the untreated group had the least weight gain,and the high expression of TMED11P did not increase the weight gain.The weight gain of the three groups was analyzed.The low expression of TMED11P treatment group had the least weight gain,and the high expression TMED11P treatment group had more weight gain.The ALT,AST,BUN,and Cre results of the treatment group were significantly lower(p<0.05),and the liver and kidney function were significantly improved.The RBC,WBC,and Lymph test results were significantly lower in the treatment group(p<0.05).To further investigate the relationship between TMED11P and pancreatic ductal adenocarcinoma cells,and the significance of TMED11P as a molecular marker in the diagnosis of pancreatic ductal adenocarcinoma cells,57 patients with pancreatic ductal adenocarcinoma were screened for further study.Studies have shown that the relative expression of TMED11P in pancreatic ductal adenocarcinoma is significantly different from that in adjacent tissues(p<0.05).There was also a correlation between patient survival time and tumor size,lymph node metastasis or TMED11P expression(p<0.05).The median survival time of the TMED11P high expression group was longer and the TMED11P low expression group was shorter.The expression level of TMED11P was positively correlated with the survival time of patients.The expression of TMED11P in tumor tissues was correlated with the prognosis of patients.Univariate analysis showed that cell differentiation,primary tumor status and TMED11P expression were correlated with patient survival time.Multivariate Cox proportional hazard regression model analysis showed that the expression level of TMED11P,the size of tumor,and the degree of tumor cell differentiation may be related to the prognosis of patients.The above results suggest that TMED11P may be a prognostic predictor of the development of pancreatic ductal adenocarcinoma.It can be combined with other indicators for better prognosis evaluation of pancreatic ductal adenocarcinoma patients,and it can also be used for doctors to choose better treatment options.reference.TMED11P may be used as a therapeutic target in the future,in combination with drugs,and better for clinical services.