MiR-21-5p Links Epithelial-Mesenchymal Transition Phenotype with Stem-Like Cell Signatures via AKT Signaling in Keloid Keratinocytes.
Keloid is the abnormal wound healing puzzled by the aggressive growth and high recurrence rate due to its unrevealed key pathogenic mechanism. MicroRNAs contribute to a series of biological processes including epithelial-mesenchymal transition (EMT) and cells stemness involved in fibrotic disease. Here, using microRNAs microarray analysis we found mir-21-5p was significantly up-regulated in keloid epidermis. To investigate the role of miR-21-5p in keloid pathogenesis, we transfected miR-21-5p mimic or inhibitor in keloid keratinocytes and examined the abilities of cell proliferation, apoptosis, migration and invasion, the expressions of EMT-related markers vimentin and E-cadherin and stem-like cells-associated markers CD44 and ALDH1, and the involvement of PTEN and the signaling of AKT and ERK. Our results demonstrated that up-regulation or knockdown of miR-21-5p significantly increased or decreased the migration, invasion and sphere-forming abilities of keloid keratinocytes, and the phenotype of EMT and cells stemness were enhanced or reduced as well. Furthermore, PTEN and p-AKT were shown to participate in the regulation of miR-21-5p on EMT phenotypes and stemness signatures of keloid keratinocytes, which might account for the invasion and recurrence of keloids. This molecular mechanism of miR-21-5p on keloid keratinocytes linked EMT with cells stemness and implicated novel therapeutic targets for keloids.
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
Li
L
Yan
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
Rui
R
Cao
Extremities Plastic and Reconstructive Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
YuanBo
Y
Liu
Comprehensive Treatment Center of Scar, Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
LianZhao
L
Wang
Auricular Plastic and Reconstructive Surgery Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
Bo
B
Pan
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
XiaoYan
X
Lv
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
Hu
H
Jiao
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
Qiang
Q
Zhuang
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
XueJian
X
Sun
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, P.R. China.
Ran
R
Xiao
D000080924:Aldehyde Dehydrogenase 1 Family; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D007627:Keloid / Q000235:genetics*; D015603:Keratinocytes / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D050697:Retinal Dehydrogenase / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D014746:Vimentin / Q000235:genetics
D015820:Cadherins; D018960:Hyaluronan Receptors; D007527:Isoenzymes; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D014746:Vimentin; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt