miR-200a, miR-200b and miR-429 are onco-miRs that target the PTEN gene in endometrioid endometrial carcinoma.
Endometrioid endometrial carcinoma (EEC) is a common malignancy of the female genital tract. However, no adequate biomarker is currently available for predicting the prognosis of this cancer. Recent studies have revealed dysregulated expression of several microRNAs (miRNAs) in various cancer tissues, and therefore, these cancer-associated miRNAs (also called onco-miRs) could be promising prognostic biomarkers of cancer progression or metastasis. In this study, in order to identify onco-miRs and their possible targets involved in EEC, we performed microarray-based integrative analyses of miRNA and mRNA expression in specimens excised from EEC lesions and adjacent normal endometrial tissues. Using integrated statistical analyses, we identified miR-200a, miR-200b and miR-429 as highly up-regulated onco-miRs in EECs. Conversely, we detected expression of a tumor-suppressor gene, phosphatase and tensin homolog (PTEN), which was predicted in silico using a miRNA-targeting mRNA prediction algorithm, as a target of the three miRNAs and which was down-regulated in EECs. Furthermore, these miRNAs were validated to target PTEN experimentally using luciferase assays and real-time polymerase chain reaction. These results suggest that the occurrence of EEC is, at least in part, mediated by miRNA-induced suppression of PTEN expression.
Department of Obstetrics and Gynecology, Nippon Medical School Main Hospital, Tokyo, Japan kyone@nms.ac.jp ishibashi@biochem.osakafu-u.ac.jp.
Koichi
K
Yoneyama
Laboratory of Biological Macromolecules, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Japan kyone@nms.ac.jp ishibashi@biochem.osakafu-u.ac.jp.
Osamu
O
Ishibashi
Department of Obstetrics and Gynecology, Nippon Medical School Main Hospital, Tokyo, Japan.
Rieko
R
Kawase
Department of Obstetrics and Gynecology, Nippon Medical School Main Hospital, Tokyo, Japan.
Keisuke
K
Kurose
Department of Obstetrics and Gynecology, Nippon Medical School Main Hospital, Tokyo, Japan.
Toshiyuki
T
Takeshita
D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics*; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*
C533896:MIRN200 microRNA, human; C546363:MIRN429 microRNA, human; D035683:MicroRNAs; D008156:Luciferases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Endometrioid endometrial cancer; PTEN; microRNA