Sequence variation among members of the miR-200 microRNA family is correlated with variation in the ability to induce hallmarks of mesenchymal-epithelial transition in ovarian cancer cells.
BACKGROUND
Epithelial-Mesenchymal Transition (EMT) is a transient and reversible (Mesenchymal-Epithelial Transition or MET) process by which epithelial cells acquire mesenchymal cell characteristics including reduced intercellular adhesion and increased cell motility. While EMT/MET has long been recognized as an essential component of early embryonic development, there is a growing body of evidence indicating that EMT/MET is also a key component of ovarian cancer (OC) metastasis. Recent findings have implicated members of the miR-200 family of microRNAs (miRNAs) in this process.


METHODS
Individual members of the miR-200 family of miRNAs were transiently over expressed in metastatic (mesenchymal-like) OC cell lines. Changes in morphology, molecular profiles and drug sensitivity were monitored relative to cells transfected with a negative control.


RESULTS
Morphological hallmarks of MET were detected in cells transfected with all miR-200 family members. Gene expression profiling demonstrated up regulation of epithelial biomarkers and down regulation of mesenchymal biomarkers in transfected cells although significant variation in molecular response and drug sensitivity was associated with different members of the miR-200 family.


CONCLUSIONS
Our results indicate that although ectopic overexpression of all members of the miR-200 family in mesenchymal-like OC cells results in morphological changes characteristic of MET, the underlying molecular changes and induced drug sensitivities are highly variable and correlated with sequence variation within the seed and non-seed regions of individual family members.
Neda
N
Jabbari
Ashley N
AN
Reavis
School of Biology, Parker H, Petit Institute of Bioengineering and Biosciences, 315 Ferst Drive, Atlanta, GA 30332-0363, USA. john.mcdonald@biology.gatech.edu.
John F
JF
McDonald
D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D020128:Inhibitory Concentration 50; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C533895:MIRN141 microRNA, human; C533896:MIRN200 microRNA, human; C546363:MIRN429 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin