title: MicroRNA-140 regulates cell growth and invasion in pancreatic duct adenocarcinoma by targeting iASPP.
abstract: MicroRNAs are ∼22 nucleotide RNAs processed from RNA hairpin structures that play important roles in regulating protein expression level via binding to mRNA, either suppressing its translation or speeding up its degradation. In humans, they regulate most protein-coding genes, including genes important in cancer and other diseases. In this study, the expression of microRNA-140 (miR-140) was demonstrated to be significantly suppressed in pancreatic duct adenocarcinoma specimens and cell lines, compared with their adjacent normal tissues. With the help of bioinformatics analysis, inhibitor of apoptosis-stimulating protein of p53 (iASPP) was identified to be a direct target of miR-140, and luciferase reporter experiment confirmed this discovery. Overexpression of miR-140 decreases the protein expressions of iASPP, ΔNp63, MMP2, and MMP9. Growth and invasion of PANC-1 cells were attenuated by overexpression of miR-140 in vitro. The suppressive effect of miR-140 on PANC-1 cell line could be partly balanced out by manual overexpression of iASPP. Above all, these findings provided insights into the functional mechanism of miR-140, suggested that the miR-140/iASPP axis may interfere with the proliferative and invasive property of pancreatic duct adenocarcinoma cells, and indicated that miR-140 could be a potential therapeutic target for pancreatic duct adenocarcinoma.
authors.affiliation: Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Gewen
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Gengwen
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Yebin
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, China liyixiong2011@hotmail.com.
authors.forename: Yixiong
authors.initials: Y
authors.lastname: Li
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; C544302:Mirn140 microRNA, human; C119612:PPP1R13L protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins
keywords: cell invasion; cell proliferation; iASPP; miR-140; pancreatic duct adenocarcinoma