Mechanisms underlying aberrant expression of miR 29c in uterine leiomyoma

Expression of miR-29c is suppressed and inversely correlated with collagen and DNMT3A in leiomyoma. The suppression of miR-29c in leiomyoma smooth muscle cells is primarily mediated by specific protein 1, NF-kB signaling, and epigenetic modification.

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Authors

Tsai-Der Chuang, Ph.D., Omid Khorram, M.D., Ph.D.

Volume 105, Issue 1, Pages 236-245

Abstract

Objective:

To determine the expression of miR-29c and its target genes in leiomyoma and the role of NF-κB, specific protein 1 (SP1), and DNA methylation in its regulation.

Design:

Experimental study.

Setting:

Academic research laboratory.

Patient(s):

Women undergoing hysterectomy for leiomyoma.

Intervention(s):

Over- and underexpression of miR-29c; blockade of transcription factors.

Main Outcome Measure(s):

MiR-29c and its target gene levels in leiomyoma and the effects of blockade of transcription factors on miR-29c expression.

Result(s):

Leiomyoma as compared with myometrium expressed significantly lower levels of miR-29c, with an inverse relationship with expression of its targets, COL3A1 and DNMT3A. Gain of function of miR-29c inhibited the expression of COL3A1 and DNMT3A at protein and mRNA levels, secreted COL3A1, and rate of cell proliferation. Loss of function of miR-29c had the opposite effect. E2, P, and their combination inhibited miR-29c in leiomyoma smooth muscle cells (LSMC). Phosphorylated NF-κB (p65) and SP1 protein expression were significantly increased in leiomyoma. SiRNA knockdown of SP1 and DNMT3A or their specific inhibitors significantly increased the expression of miR-29c, accompanied by the inhibition of cellular and secreted COL3A1 in siRNA-treated cells. Knockdown of p65 also induced miR-29c expression but had no effect on COL3A1 expression.

Conclusion(s):

MiR-29c expression is suppressed in leiomyoma, resulting in an increase in expression of its targets COL3A1 and DNMT3A. The suppression of miR-29c in LSMC is primarily mediated by SP1, NF-κB signaling, and epigenetic modification. Collectively, these results indicate a significant role for miR-29c in leiomyoma pathogenesis.

Read the full text at: http://www.fertstert.org/article/S0015-0282(15)01937-8/fulltext


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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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