Mechanisms Underlying Aberrant Expression of Mir-29c in Uterine Leiomyoma  

Oleh:

Tsai-Der Chuang ; Khorram, Omid

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 105 no. 01 (Jan. 2016), page 236-245.
Topik: Leiomyoma; miR-29c; COL3A1; DNMT3A; SP1
Fulltext: F02 v105 n1 p236 kelik2016.pdf (2.51MB)

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Objective: To determine the expression of miR-29c and its target genes in leiomyoma and the role of NF-?B, 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-?B (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-?B signaling, and epigenetic modification. Collectively, these results indicate a significant role for miR-29c in leiomyoma pathogenesis.

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