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• W3092881834 abstract "Uterine fibroids (UFs) are monoclonal tumors arising in the myometrium, and are the most common tumors of reproductive age women. Although UFs impact the quality of life of women of all ethnicities, this disease is more prevalent and more severe among African American (AA) women compared with Caucasian (CC) women. To date, little is known about the mechanism of this ethnic disparity. An increasing body of evidence demonstrates that abnormal genetic and epigenetic alterations contribute to development of UFs. Recently, another layer of gene regulation at the RNA level, i.e., RNA epitranscriptomics has gained increased attention and interest in the research community. To date, over 150 post-transcriptional modifications of RNA have been identified. Among them, N6-methyladenosine (m6A) is the most abundant, dynamic and reversible modification involved in many biological events and diseases. However, the knowledge of epitranscriptomics in UFs is completely lacking. DESIGN: Laboratory research studies using human myometrium and UFs tissues Human UFs (n=14) and adjacent myometrium tissues (MyoF, n=14) were collected at time of hysterectomy. Western blot (WB) was performed to determine the protein levels of m6A writers (METTL3, WTAP, VIRMA, and RBM15) and Readers (YTHDC1, and YTHDF2). Student’s t-test was used to determine the significant difference. Our studies demonstrated that 62.5% (5 of 8) of AA patients exhibited an upregulation of METTL3 in UFs compared to MyoF while only 16.7% (1 of 6) of CC patients showed upregulation of METTL3. On the other hand, 37.5% AA women and 83.3% CC women showed downregulation of METTL3 in UFs compared to MyoF respectively. These data suggest that this key m6A writer may contribute to the ethnic disparities of UFs. In addition, we measured the adaptors of m6A writers (WTAP, VIRMA, RBM15), no trend of differential expression between UFs and MyoF in both AA and CC population was observed. Next, we determined the protein levels of key m6A readers YTHDC1 and YTHDF2, and demonstrated that a significant upregulation of YTHDC1 and YTHDF2 in UFs over MyoF was found (p<0.05) in AA women, but not in CC women. Moreover, 87.5% (7/8) of AA exhibited upregulation of YTHDC1 and YTHDF2 respectively, while only 33.3% (2/6) and 50% (3/6) of CC showed upregulation of YTHDC1 and YTHDF2 respectively. These results suggest that abnormal epitranscriptomic alteration, e.g. the METTL3-m6A-YTHDC1/YTHDF2 signaling axis could be involved not only in the pathogenesis of UFs, but also contributing to increased UF prevalence and burden in AA women. Further studies are needed to determine the expression patterns of m6A regulators in a large sample size, and characterize the role of m6A regulators in pathogenesis of UFs." @default.
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• W3092881834 date "2020-09-01" @default.
• W3092881834 modified "2023-09-29" @default.
• W3092881834 title "N6-METHYLADENOSINE REGULATORS IN PREVALENCE AND BURDEN OF BLACK WOMEN IN UTERINE FIBROIDS" @default.
• W3092881834 doi "https://doi.org/10.1016/j.fertnstert.2020.08.655" @default.
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