MiR-145 regulates epithelial to mesenchymal transition of breast cancer cells by targeting Oct4.
MiR-145 could regulate tumor growth, apoptosis, migration, and invasion. In our present study, we investigated its role in epithelial-mesenchymal transition (EMT). Expression of miR-145 was decreased in breast tumor tissues at T3&4 stages in comparison with those at T1&2. Over-expression of miR-145 mimics enhanced protein levels of E-cadherin and dampened those of α-SMA and Fibronectin, indicative of its inhibitory role in EMT occurrence. Mechanistic studies showed that miR-145 mimics inhibited Oct4 expression and miR-145 inhibitor enhanced it. Over-expression of Oct4 reversed miR-145-regulated expression of EMT markers, suggesting that Oct4 mediated the inhibitory effects of miR-145. MiR-145 could inhibite the expression of Snail, ZEB1, and ZEB2, while over-expression of Oct4 rescued the effects. Furthermore, Oct-4 induced over-expression of transcription factor Snail, ZEB1 and ZEB2 was mediated by β-catenin. Expression of Slug and Twist were not altered by miR-145/Oct4. Taken together, our results have revealed a novel role of miR-145 on EMT. It inhibits EMT by blocking the expression of Oct4, and downstream transcriptional factors, Snail, ZEB1 and ZEB2.
Tianjin Medical University, Research Center of Basic Medical Sciences, Tianjin, China.
Jiajia
J
Hu
Hua
H
Guo
Hongyan
H
Li
Yan
Y
Liu
Jingjing
J
Liu
Liwei
L
Chen
Jin
J
Zhang
Ning
N
Zhang
D000199:Actins / Q000096:biosynthesis; D000906:Antibodies / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D014945:Wound Healing; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
D000199:Actins; D000906:Antibodies; D005353:Fibronectins; D018398:Homeodomain Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012097:Repressor Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1