Open AccessDefining fallopian tube‐derived miRNA cancer signatures
Author(s) -
Dejene Selam B.,
Ohman Anders W.,
Du Wei,
Randhawa Deepinder,
Bradley Anand,
Yadav Niraj,
Elias Kevin M.,
Dinulescu Daniela M.,
Setlur Sunita R.
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2416
Subject(s) - microrna , pten , ovarian cancer , doxycycline , cancer , cancer research , fallopian tube , biology , fallopian tube cancer , gene , medicine , oncology , apoptosis , genetics , gynecology , pi3k/akt/mtor pathway , antibiotics
Background MicroRNAs have recently emerged as promising circulating biomarkers in diverse cancer types, including ovarian cancer. We utilized conditional, doxycycline‐induced fallopian tube (FT)‐derived cancer models to identify changes in miRNA expression in tumors and plasma, and further validated the murine findings in high‐grade ovarian cancer patient samples. Methods We analyzed 566 biologically informative miRNAs in doxycycline‐induced FT and metastatic tumors as well as plasma samples derived from murine models bearing inactivation of Brca , Tp53 , and Pten genes. We identified miRNAs that showed a consistent pattern of dysregulated expression and validated our results in human patient serum samples. Results We identified six miRNAs that were significantly dysregulated in doxycycline‐induced FTs ( P < .05) and 130 miRNAs differentially regulated in metastases compared to normal fallopian tissues ( P < .05). Furthermore, we validated miR‐21a‐5p, miR‐146a‐5p, and miR‐126a‐3p as dysregulated in both murine doxycycline‐induced FT and metastatic tumors, as well as in murine plasma and patient serum samples. Conclusions In summary, we identified changes in miRNA expression that potentially accompany tumor development in murine models driven by commonly found genetic alterations in cancer patients. Further studies are required to test both the function of these miRNAs in driving the disease and their utility as potential biomarkers for diagnosis and/or disease progression.