The Role Of ARVCF Or NMIIA In Pancreatic Cancer

Section ? The role of ARVCF in pancreatic cancerPrevious studies have shown that ARVCF is highly expressed in lung cancer,and its expression is related to the pathological staging,lymph node metastasis and prognosis of the patients.However,its role in the development of pancreatic cancer is not clear,and the regulatory mechanism is not reported.This study aims to explore the key role and molecular biological mechanism of ARVCF in the occurrence and development of pancreatic cancer,and provides an important theoretical foundation and potential new targets for inhibiting or delaying the occurrence of recurrence and metastasis of pancreatic cancer.We used tissue microarray to investigate the the expression of ARVCF in pancreatic cancer tissues and paracancerous tissues.ARVCF knockdown with sh RNA was performed to investigate the role of ARVCF on cell proliferation,migration and invasion,and their effects on downstream gene expression in PANC-1 cells.The subcutaneous tumor bearing experiment in nude mice was used to verify the effect of ARVCF on cell proliferation in vivo.The results showed that ARVCF was highly expressed in the pancreatic cancer tissue compared with the paracancerous tissue,and the expression was related to the prognosis of the pancreatic cancer patients.with ARVCF knocking down,the cell proliferation and clone formation were inhibited by inducing the cell cycle arrest of pancreatic cancer cells,and the migration and invasion of pancreatic cancer cells were inhibited.In vivo,experiments also showed that the volume of the subcutaneous tumorigenesis in nude mice decreased significantly and the expression of proliferation markers such as Ki-67 and PCNA in subcutaneous tumor decreased with the knockdown of ARVCF.After overexpression of ARVCF,the proliferation,clone formation of pancreatic cancer cells were promoted.Further study found that by ARVCF knockdown and overexpression of ARVCF can regulate STAT3 nuclear import and transcriptional activity and thus affect the activity of STAT3 pathway.The ectopic expression of STAT3 can reverse the inhibitory effect of ARVCF knockdown on the proliferation of pancreatic cancer cells.Stattic,an inhibitor of STAT3,can reduce the effect of ARVCF on the proliferation of pancreatic cancer cells.In summary our results show that ARVCF regulated the biological behavior of pancreatic cancer by affecting the activation of STAT3.In addition,we demonstrate for the first time that the expression of ARVCF protein was regulated by TGF-?.Our study elucidated the biological mechanism of ARVCF in pancreatic cancer and provided important theoretical basis and potential new targets for the prevention and treatment of pancreatic cancer.Section ? The role of NMIIA in pancreatic cancerNon-muscle myosin ? proteins play an important role in cell cytokinesis and cell migration.Among its family,non-muscle myosin IIA(NMIIA)belongs to the main isoform of Non-muscle myosin II protein.The role and underlying regulatory mechanisms of NMIIA in pancreatic cancer remain elusive.We aimed to study NMIIA expression,function,regulation mechanisms pancreatic cancer(PC)cells and related clinical implication in PC patients.Here,we observed that NMIIA was much higher expressed in tumor tissues compared with adjacent normal tissues,and prognosis of the PC patients with higher NMIIA expression was worse.In vitro and in vivo studies,NMIIA knockdown significantly inhibited cell proliferation,migration,invasion and induced G0/G1 phase arrest.Furthermore,NMIIA knockdown inhibited sphere formation and decreased the m RNA levels of main stem markers,such as CD44,CD24,CD133,Nanog and Sox2.Furthermore,NMIIA knockdown significantly attenuated the TGF-?-induced EMT process,evidenced by the upregulation of E-cadherin and downregulation of N-cadherin,vimentin,resulting in the inhibition of TGF-?-induced cell migration.Mechanistically,the inhibition effects by NMIIA knockdown could be caused by the inactivation of Wnt/?-catenin signaling.Moreover,NMIIA activity is modulated by the MEK/ERK signaling in PC cells.In conclusion,NMIIA can facilitate the Wnt/?--catenin signaling pathway that promotes tumor progression and EMT in PC.