Differential expression of microRNAs in myometrium and leiomyomas and regulation by ovarian steroids.
Given the emerging roles of microRNAs (miRNAs) as key regulator of mRNA stability we assessed their expression profile in paired myometrium and leiomyoma, their isolated smooth muscle cells (MSMC and LSMC), a spontaneously transformed leiomyoma smooth muscle cells (T-LSMC) and SK-LMS-1, a leiomyosarcoma cell line using microarray and real time PCR. Based on global normalization of expression values of 385 miRNAs and statistical analysis (anova), 91 miRNAs were expressed above the threshold levels in myometrium, with a progressive decline in numbers in leiomyomas, MSMC, LSMC, T-LSMC and SK-LMS-1 (P<0.05). We selected and validated the expression of miR-20a, miR-21, miR-26a, miR-18a, miR-206, miR-181a and miR-142-5p and found their differential expression in tissue and cell-specific manners (P<0.05). Treatments of MSMC and LSMC with 17beta estradiol and medroxyprogesterone acetate (10(-8)M), or ICI-182780 and RU-486 (10(-6)M) resulted in differential regulation of these miRNAs (P<0.05). In conclusion, the expression of a number of miRNAs in myometrium and leiomyoma with their progressive aberrant from normal MSMC into LSMC, transformed and cancerous stage, suggests that miRNAs and their regulation by ovarian steroids play a key role in pathogenesis of leiomyoma through gene expression stability.
Pan
Qun
Q
Department of Obstetrics and Gynecology, University of Florida, Gainesville, FL 32610, USA.
Luo
Xiaoping
X
Chegini
Nasser
N
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D035683:MicroRNAs / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000494:pharmacology*; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D006727:Hormone Antagonists; D035683:MicroRNAs; D012333:RNA, Messenger; D013256:Steroids; D000077267:Fulvestrant; D015735:Mifepristone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate