It is well established that microRNA (miRNA) expression profiles are altered in patients with polycystic ovary syndrome (PCOS). In addition, abnormal transforming growth factor beta (TGFB) signaling in granulosa cells is related to the pathological conditions of PCOS. However, the function of dysregulated miRNAs in PCOS is still unclear. In this study, we aimed to elucidate the roles of specific miRNAs in PCOS. We collected follicular fluid from 46 patients with PCOS and 32 healthy controls. Granulosa cells (GCs) were separated and the levels of six candidate miRNAs were determined by quantitative RT-PCR. The direct targets of three dysregulated miRNAs were predicted using bioinformatic tools and confirmed using a dual luciferase assay and immunoblotting. The biological function of three dysregulated miRNAs in primary GCs was determined using a cell proliferation assay and flow cytometry. We found that miR-423 expression was downregulated (P = 0.038), and the levels of miR-33b (P = 0.032) and miR-142 (P = 0.021) were upregulated in GCs from patients with PCOS, compared to controls. miR-423 directly repressed SMAD family member 7 (SMAD7) expression, while transforming growth factor beta receptor 1 (TGFBR1) was a direct target of both miR-33b and miR-142. An RNA oligonucleotide mixture containing miR-423 inhibitor, miR-33b mimic, and miR-142 mimic repressed TGFB signaling, promoted cell proliferation (P = 0.0098), repressed apoptosis (P = 0.027), and increased S phase cell numbers (P = 0.0036) in primary cultures of GCs, compared to the cells treated with a sequence scrambled control RNA oligonucleotide. This study unveiled the possible roles of three miRNAs in PCOS and might provide candidate biomarkers for PCOS diagnosis while in vivo functional studies, using transgenic or knockout mouse models, are expected to confirm the roles of dysregulated miRNAs in the pathogenesis of PCOS.
A simple, efficient, and general α-prenylation approach for the synthesis of a variety of α-prenylated alcohols has been successfully developed. A wide range of α-prenylated alcohol derivatives could be obtained in good yields by highly α-regioselective zinc-mediated prenylation of various aldehydes and ketones with prenyl bromide at 120 °C in HMPA. By simply altering the reaciton solvent and temperature, the method allows the achievement of a highly notable opposite regiocontrol, providing the expected regiochemical product. The method provides a convenient route for the direct α-prenylation of carbonyl compounds in a highly α-regioselective manner using a cheap and convenient mediator. Two possible pathways are proposed to account for the formation of these synthetically difficult-to-obtain molecules.
A highly α-regioselective prenylation of imines has been successfully developed. The efficiency of this approach is confirmed by a wide range of imines including N- and C-aryl aldimines, N-alkyl aldimines, C-alkyl aldimines, and N- and C-aryl ketimines. The approach uses prenyl bromide as the prenyl source and inexpensive and convenient zinc as the mediator as well as environmentally benign 1,3-dimethyl-2-imidazolidinone (DMI) as the solvent.
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