| Pancreatic cancer(PC)in clinical is one of the most cancerous digestive system neoplasms.In the last year's survey of adult cancerous neoplasms in China,the incidence rate of pancreatic malignancies ranked eighth,and mortality rate ranked seventh.Pancreatic cancer has been building-up definitely in the past decade.The extremely low survival rate in clinical of pancreatic cancer is mainly due to the inapparent early clinical symptoms in patients with pancreatic cancer.When the tumor is diagnosed,it has been accompanied with extensive metastasis of peripheral organs,and the chance of radical operation is lost.As a result of the lack of early diagnosis and available treatment,most of sick patients have a median survival time be fewer than half a year.Despite a lot of efforts in the improvement of surgical methods and preoperative adjuvant therapy,the mortality rate of progressive PC has remained high in the past decade.Although some factors related to PC diagnosis or prognoses have been found in previous studies,the improvement of prognosis and overall survival rate of patients is not significant after clinical observation.Therefore,it has far-reaching clinical significance to explore the cancerous behavior of PC and the principle of tumor development at the cancerous level.Our research will provide valid testimony and guidance for early diagnosis,finding new therapeutic targets,predicting prognosis and available treatment of PC.LNC(long non coding)RNAs are a category of more than 200 nucleotides in length.More and more evidences show that although Lnc RNAs have no capable of possessing the ability to encoding proteins,lnc RNAs may participate in a multiple of gene measure processes such as transcription,epigenetic and post transcriptional regulation.Lncrnas are broadly expressed in human cells and participate in numerous biological events.These biological behaviors include proliferation,differentiation,apoptosis and regulation in cell-cycle.It has become the most popular research areas of functional genomics after messenger RNA and micro RNA.ABHD11-AS1 is an LNC RNA oncogene located at 7q11.23.Previously,it was identified by the names of long intergenic nonprotein coding RNA 35(linc00035)and Williams Beuren syndrome chromosome region 26(wbscr26).ABHD11-AS1 has been found be dysregulated in a lot of neoplasms,such as bladder cancer,endometrial neoplasm and epithelial ovarian neoplasm.The expression level of abhd11-as1 in gastric neoplasm increased conspicuously.The accurate specificity of the expression makes it a potential clinical marker of gastric neoplasm recently.Abhd11-as1 was also discovered to be expressed in PC,but its specific expression,mechanism of action and practicability of clinical utilization have not been covered.Based on these relevant background,our laboratory plans to detect the expression of abhd11-as1 in PC at the tissue level;analyze the relationship between abhd11-as1 and the prognosis of patients at the clinical level;at the same time,explore the regulatory mechanism and action pathway of abhd11-as1 in PC at the molecular level,so as to further explore if abhd11-as1 can become a novel markers of oncology in PC.And we will explore the feasibility of PC as a new reminder for clinical diagnosis in early stage and targeted therapy.Methods1.In PC and paracancerous normal pancreatic tissue,we measured the expression level of abhd11-as1 and the relationship between the expression standard of abhd11-as1 by QRT PCR,and analyze clinical factors and prognosis.2.In PC cell line,the expression of abhd11-as1 was measured by QRT PCR.We constructed the abhd11-as1 interference plasmid,which was packaged by lentivirus,and then transfected the PC cell line with relatively high expression of abhd11-as1.Then we detected the expression of abhd11-as1 by q RT-PCR.3.We measured the influences of interfering with the expression of abhd11-as1 gene in vitro on the proliferation,apoptosis,migration,invasion and EMT related proteins using method such as MTT,flow cytometry,scratch test,clone formation test,Transwell test and Western blot of PC cells.4.We use Western blot to further test and verify the influences of abhd11-as1 on PC cells through the abnormal expression of PI3 K / Akt pathway.Results1.We discovered that the expression of ABHD11-AS1 was obviously more than that in normal tissues in PC.ABHD11-AS1's high expression is related to TNM stage,tumor differentiation and distant metastasis in PC.Kaplan Meier analysis showed that high expression level of ABHD11-AS1 indicated worse survival rate and prognosis.Furthermore,univariate and multivariate analysis were used and the conclusion discovered that the expression of ABHD11-AS1 was an important independent factor related to low overall survival.2.Our outcomes discovered that the interference of ABHD11-AS1 gene expression in vitro experiment could inhibit the proliferation of PC cells,promote the apoptosis of PC cells,reduce the formation of cell clones,slow down the migration and invasion ability of pancreatic cancer cells and the expression of EMT related proteins.3.Our conclusions in vitro showed that the expression in PC cells of phosphorylated(P)AKT and phosphorylated(P)PI3K decreased significantly using Western blot results of after further interference with the expression of ABHD11-AS1 gene,but the expression of AKT and PI3 K in PC cells was not affected.Conclusion1.In PC tissue,the obvious expression of ABHD11-AS1 has close link to TNM stage,tumor differentiation and distant metastasis,which can be used as an independent risk factor for poor prognosis of PC.2.In vitro,ABHD11-AS1 can enhance the proliferation,migration,invasion and metastasis of PC cells,meanwhile,it can restrain the apoptosis of PC cells and interfere the expression of EMT related proteins.3.Abhd11-as1 may further affect the malignant biological behavior of PC by activating PI3 K / Akt signaling pathway. |
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