miR-30d Blocked Transforming Growth Factor β1-Induced Epithelial-Mesenchymal Transition by Targeting Snail in Ovarian Cancer Cells.
OBJECTIVE
MicroRNAs (miRs) are essential regulators of gene expression by suppressing translation or causing degradation of target mRNA. Growing evidence sheds light on the crucial roles of miR dysregulation in cancer development and progression. In this study, we focused on the role of miR-30d in transforming growth factor β1 (TGF-β1)-initiated epithelial-mesenchymal transition (EMT) in ovarian cancer cells.


METHODS
Transforming growth factor β1 (10 ng/mL) was used to initiate EMT in SKOV3 and 3AO cells. The expression of miR-30 family members was determined by quantitative real-time polymerase chain reaction. Messenger RNA and protein levels of E-cadherin, N-cadherin, vimentin, and Snail were detected by quantitative real-time polymerase chain reaction and Western blot, respectively. Cell migration and invasion capacities were evaluated by Transwell chamber assay. Luciferase activity assay was performed to verify the direct inhibition of Snail by miR-30d.


RESULTS
MiR-30b, MiR-30c, and MiR-30d were down-regulated during TGF-β1-induced EMT in SKOV3 and 3AO ovarian cancer cells. Restoration of miR-30d by miR-30d mimic reversed TGF-β1-induced EMT phenotypes including the morphological changes, expression pattern of molecular markers (E-cadherin, N-cadherin), and migratory and invasive capabilities in ovarian cancer cells. Furthermore, Snail was identified as the direct target of miR-30d.


CONCLUSIONS
Our results revealed that miR-30d functioned as a suppressor of ovarian cancer progression by decreasing Snail expression and thus blocking TGF-β1-induced EMT process, suggesting the potentiality of miR-30d analogs to be used as therapeutics for ovarian cancer.
Centers for *Translational Medicine and †Laboratory Medicine, the First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, People's Republic of China.
Zhongxue
Z
Ye
Le
L
Zhao
Jie
J
Li
Wei
W
Chen
Xu
X
Li
D020413:3' Untranslated Regions / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010051:Ovarian Neoplasms; D012333:RNA, Messenger / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D015820:Cadherins; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D014746:Vimentin