Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women.
The objective of this study, a parallel study to global gene expression profiling, was to identify dysregulated microRNAs (miRNAs) associated with endometrioid endometrial adenocarcinoma (EEC), examine their correlation with clinico-pathological characteristics and identify predicted target genes of the dysregulated miRNAs. Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), profiling of miRNA expression was performed in 30 EECs and 22 normal counterparts in which genome-wide gene expression had been previously profiled and reported. Clustering analysis identified 30 miRNAs which were significantly dysregulated in EEC. The expression of a sub-group of miRNAs was significantly correlated with clinico-pathological characteristics including stage, myometrial invasion, recurrence and lymph node involvement. By searching for predicted miRNA targets that were linked to the dysregulated genes previously identified, 68 genes were predicted as candidate targets of these 30 dysregulated miRNAs. miR-205 was significantly overexpressed in EECs compared with normal controls. After transfection of a miR-205 inhibitor, the expression of miR-205 in endometrial cancer cell line RL95-2 cells decreased whereas its predicted target gene, JPH4, showed increased protein expression. JPH4 seems to be a real miR-205 target in vitro and in vivo, and a candidate tumor suppressor gene in EEC. Based on this study in EEC, miRNAs predicted to be involved in tumorigenesis and tumor progression have been identified and placed in the context of the transcriptome of EEC. This work provides a framework on which further research into novel diagnosis and treatment of EEC can be focused.
Chung
Tony K H
TK
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.
Cheung
Tak-Hong
TH
Huen
Ngar-Yee
NY
Wong
Katherine W Y
KW
Lo
Keith W K
KW
Yim
So-Fan
SF
Siu
Nelson S S
NS
Wong
Yin-Mei
YM
Tsang
Po-Ting
PT
Pang
Man-Wah
MW
Yu
Mei-Yun
MY
To
Ka-Fei
KF
Mok
Samuel C
SC
Wang
Vivian W
VW
Li
Chen
C
Cheung
Albert Y K
AY
Doran
Graeme
G
Birrer
Michael J
MJ
Smith
David I
DI
Wong
Yick-Fu
YF
D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006723:Hong Kong; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D017698:Postmenopause; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values
D035683:MicroRNAs; D012334:RNA, Neoplasm