The team, using data from The Cancer Genome Atlas, zeroed in on the biochemical interplay between a transcription factor, STAT3, which has been associated with poor outcome in ovarian cancer patients when present in high levels, and a microRNA called miR551b. This little-studied microRNA now has been shown to impact STAT3 protein levels, contributing to resistance to cell death and increased proliferation of cancer cells both in vivo and in vitro.
To explore the potential of miR551b as a therapeutic target, the research team treated mice with an anti-miR551b therapy, twice a week for a month and observed markedly decreased tumor growth.
"Our results demonstrate the therapeutic potential of anti-miR551b in treating ovarian cancers with high levels of miR551b," said the author. "Remarkably, this study shows that microRNAs can also up regulate the expression of key cancer genes directly. This suggests that the mechanisms by which microRNAs regulate cellular function are much broader than was generally accepted. Future studies will need to examine the activity of combination therapy of anti-miR551b with other therapeutic interventions."
They show that miR551b-3p upregulates STAT3 protein levels, and STAT3 is required for the effects of miR551b-3p on cell proliferation. Rather than decreasing levels of target mRNA as expected, authors demonstrate that miR551b-3p binds a complementary sequence on the STAT3 promoter, recruiting RNA polymerase II and the TWIST1 transcription factor to activate STAT3 transcription, and thus directly upregulates STAT3 expression.
Furthermore, anti-miR551b reduced STAT3 expression in ovarian cancer cells in vitro and in vivo and reduced ovarian cancer growth in vivo. Together, our data demonstrate a role for miR551b-3p in transcriptional activation. Thus, miR551b-3p represents a promising candidate biomarker and therapeutic target in ovarian cancer.
Micro RNA, a promising ovarian cancer biomarker and therapeutic target
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