miR-18a counteracts AKT and ERK activation to inhibit the proliferation of pancreatic progenitor cells.
Activation of endogenous stem/progenitor cells to repair injured tissues is an ideal option for disease treatment. However, adult pancreatic progenitor cells remain in a quiescent state in vivo. Thus, it is difficult to stimulate proliferation and differentiation in these progenitor cells, and the cause remains elusive. miR-17-92 cluster miRNAs are highly conserved in mammals and are expressed in multiple tissue stem/progenitor cells, but their role in pancreatic progenitor cells are less well known. In the present study, we demonstrate that miR-18a, but not the other members of the miR-17-92 gene cluster, inhibits the proliferation of pancreatic progenitor cells in vitro and ex vivo. miR-18a inhibits proliferation of adult pancreatic progenitor cells through arresting the cell cycle at G1 stage, indicating that miR-18a plays a role in keeping the adult pancreatic progenitor cells in quiescence. miR-18a inhibits pancreatic progenitor proliferation by targeting the gene expressions of connective tissue growth factor (CTGF), neural precursor cell expressed, developmentally down-regulated 9 (Nedd9), and cyclin dependent kinase 19 (CDK19), as well as by suppressing activation of the proliferation-related signaling pathways phosphatidylinositol 3-kinase-protein kinase B (PI3K/AKT) and extracellular signal-regulated kinase (ERK).
College of Life Science, Northeast Forestry University, Harbin, 150040, China.|College of Life Sciences and Agriculture and Forestry, Qiqihar University, Qiqihar, 161006, China.
Xuyan
X
Li
College of Life Science, Northeast Forestry University, Harbin, 150040, China.|Faculty of Health Sciences, University of Macau, Taipa, Macau, People's Republic of China.
Zhenwu
Z
Zhang
College of Life Science, Northeast Forestry University, Harbin, 150040, China.
Yunchao
Y
Li
College of Life Science, Northeast Forestry University, Harbin, 150040, China.
Yicheng
Y
Zhao
College of Life Science, Northeast Forestry University, Harbin, 150040, China.
Wenjun
W
Zhai
College of Life Science, Northeast Forestry University, Harbin, 150040, China.
Lin
L
Yang
College of Life Science, Northeast Forestry University, Harbin, 150040, China.
Delin
D
Kong
College of Life Science, Northeast Forestry University, Harbin, 150040, China.
Chunyan
C
Wu
College of Life Science, Northeast Forestry University, Harbin, 150040, China.
Zhenbao
Z
Chen
College of Life Science, Northeast Forestry University, Harbin, 150040, China.
Chun-Bo
CB
Teng
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D005810:Multigene Family; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*
D020413:3' Untranslated Regions; D015415:Biomarkers; C552691:MIRN18 microRNA, mouse; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases