title: MicroRNA-410 functions as a tumor suppressor by targeting angiotensin II type 1 receptor in pancreatic cancer.
abstract: MicroRNAs (miRNAs) act as key regulators of gene expression in diverse biological processes and are intimately involved in tumorigenesis. However, the underlying molecular mechanisms of miR-410 in pancreatic cancer remain poorly understood. In this study, we found that miR-410 overexpression suppressed pancreatic cancer cell growth in vitro and in vivo as well as cell invasion and migration. miR-410 also resulted in G1/S cell-cycle arrest. We then showed that angiotensin II type 1 receptor (AGTR1) was a direct target of miR-410, with miR-410 suppressing AGTR1 expression levels. In contrast, inhibition of miR-410 increased the expression of AGTR1. Silencing of AGTR1 inhibited cell growth and invasion, similar to miR-410 overexpression. In addition, we found that the induction of vascular endothelial growth factor and the activation of the ERK signaling pathway by angiotensin II were blocked by miR-410, similar to the angiotensin II inhibitor losartan. miR-410 overexpression inhibited angiogenesis in mice through the repression of CD31 expression. ERK pathway knockdown suppressed pancreatic cancer cell proliferation, invasion, and angiogenesis. Finally, we found that miR-410 was downregulated in pancreatic cancer tissues compared to adjacent nontumor tissues, whereas AGTR1 was upregulated in pancreatic cancer tissues. Pearson correlation analysis showed that miR-410 and AGTR1 were inversely expressed. In conclusion, our data indicate that miR-410 suppresses pancreatic cancer growth, cell invasion, migration, and angiogenesis via the downregulation of AGTR1, acting as a tumor-suppressive miRNA. In addition, our results suggest that miR-410 is a potential diagnostic biomarker and therapeutic target for patients with pancreatic cancer.
authors: Department of General Surgery, Tianjin First Central Hospital, Tianjin, China.
authors: Rende
authors: R
authors: Guo
authors: Jianhua
authors: J
authors: Gu
authors: Zhibin
authors: Z
authors: Zhang
authors: Yi
authors: Y
authors: Wang
authors: Chuan
authors: C
authors: Gu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism* / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014945:Wound Healing / Q000187:drug effects
chemical_list: D017931:DNA Primers; C568527:MIRN410 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D044140:Receptor, Angiotensin, Type 1; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue
keywords: Angiotensin II Type 1 Receptor (AGTR1); miR-410; microRNA; tumor suppressor