Characterization of MicroRNA-200 pathway in ovarian cancer and serous intraepithelial carcinoma of fallopian tube

Autor: Pui-Wah Choi, William R. Welch, Kuan-Chun Huang, Xiaoyan Ni, Yilan Zhou, Kathleen Hasselblatt, Michael G. Muto, Shu-Kay Ng, Junzheng Yang, Ross S. Berkowitz, Shu-Wing Ng
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Pathology
Fallopian tube tumors
endocrine system diseases
Expression analysis
CDH1
0302 clinical medicine
Ovarian tumors
Gene Regulatory Networks
Ovarian Neoplasms
biology
Effector
MicroRNA
Transfection
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
female genital diseases and pregnancy complications
Gene Expression Regulation
Neoplastic
Serous fluid
medicine.anatomical_structure
Oncology
Organ Specificity
030220 oncology & carcinogenesis
Female
RNA Interference
Carcinoma in Situ
Research Article
endocrine system
medicine.medical_specialty
lcsh:RC254-282
03 medical and health sciences
Ovarian Epithelial Tumor
Cell Line
Tumor
microRNA
Biomarkers
Tumor
Genetics
medicine
Humans
RNA
Messenger
Fallopian Tubes
Neoplasm Staging
Gene Expression Profiling
medicine.disease
Cystadenocarcinoma
Serous
MicroRNAs
030104 developmental biology
biology.protein
Cancer research
Neoplasm Grading
Ovarian cancer
Fallopian tube
Zdroj: BMC Cancer
BMC Cancer, Vol 17, Iss 1, Pp 1-12 (2017)
ISSN: 1471-2407
Popis: Background Ovarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors. Methods RNA prepared from ovarian and fallopian tube epithelial and stromal fibroblasts was subjected to quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to determine the expression of miR-200 families, target and effector genes and analyzed for clinical association. The effects of exogenous miR-200 on marker expression in normal cells were determined by qRT-PCR and fluorescence imaging after transfection of miR-200 precursors. Results Ovarian epithelial tumor cells showed concurrent up-regulation of miR-200, down-regulation of the four target genes (ZEB1, ZEB2, TGFβ1 and TGFβ2), and up-regulation of effector genes that were negatively regulated by the target genes. STIC tumor cells showed a similar trend of expression patterns, although the effects did not reach significance because of small sample sizes. Transfection of synthetic miR-200 precursors into normal ovarian surface epithelial (OSE) and fallopian tube epithelial (FTE) cells confirmed reduced expression of the target genes and elevated levels of the effector genes CDH1, CRB3 and EpCAM in both normal OSE and FTE cells. However, only FTE cells had a specific induction of CA125 after miR-200 precursor transfection. Conclusions The activation of the miR-200 pathway may be an early event that renders the OSE and FTE cells more susceptible to oncogenic mutations and histologic differentiation. As high-grade serous ovarian carcinomas (HGSOC) usually express high levels of CA125, the induction of CA125 expression in FTE cells by miR-200 precursor transfection is consistent with the notion that HGSOC has an origin in the distal fallopian tube. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3417-z) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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