title: MicroRNA regulation of progesterone receptor in breast cancer.
abstract: Hormone receptor status is of significant value when deciding on anti-estrogenic adjuvant therapy for breast cancer tumors. However, while estrogen receptor (ER) regulation was intensively studied, the regulation of progesterone receptor (PR) levels has not been extensively investigated. MicroRNAs (miRNAs, miRs) are post-transcriptional negative regulators of gene expression involved in diverse cellular processes. The aim of this study was to identify miRNAs that regulate PR in breast cancer.We mapped potential miRNA binding sites for miR-181a, miR-23a and miR-26b on PR mRNA and demonstrated a direct regulation of PR by these three miRNAs by in-vitro Luciferase binding assays. Over-expression of each miRNA in MCF-7 cells resulted in a reduction in the expression levels of PR mRNA. Then, expression levels of these miRNAs were measured in Formalin-Fixed, Paraffin-Embedded (FFPE) samples of 29 ER-positive breast cancer tumors and adjacent normal breast tissues. A significant reciprocal correlation between PR mRNA and the miRNA levels were identified suggesting a role for miR-181a, miR-23a and miR-26b in PR regulation in breast cancer. Moreover, the average expression fold-changes of the three miRNAs between cancerous and normal tissues displayed an opposite trend when analyzing according to Immuno-histochemistry(IHC) status. Furthermore, miR-181a and miR-26b were found to be over-expressed in most tumor tissues supporting their role in ER-positive breast cancer development. We conclude that miR-181a, miR-23a and miR-26b act as negative regulators of PR expression in ER-positive breast cancer. The diagnostic and prognostic potential of these miRNAs in breast cancer should be further evaluated.
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Gilam
authors.affiliation: Oncology Department, Galilee Medical Center, Nahariya, Israel.|Faculty of Medicine, Bar Illan University, Zefad, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Shai
authors.affiliation: Hillel Yaffe Medical Center, Hedera, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Ashkenazi
authors.affiliation: Oncology Department, Galilee Medical Center, Nahariya, Israel.|Faculty of Medicine, Bar Illan University, Zefad, Israel.
authors.forename: Liat Appel
authors.initials: LA
authors.lastname: Sarid
authors.affiliation: Oncology Department, Galilee Medical Center, Nahariya, Israel.
authors.forename: Assi
authors.initials: A
authors.lastname: Drobot
authors.affiliation: Oncology Department, Galilee Medical Center, Nahariya, Israel.|Faculty of Medicine, Bar Illan University, Zefad, Israel.
authors.forename: Amitai
authors.initials: A
authors.lastname: Bickel
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger; D011980:Receptors, Progesterone
keywords: breast cancer; miR-181a; miR-23a; microRNA; progesterone receptor