MiR-4261 Regulates Granulosa Cell Proliferation Mediated by Progesterone via FZD5 in Human Ovarian Granulosa Cell Line.
- 1Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China.
Abstract
Background: The effect of different controlled ovarian hyperstimulation (COH) protocols on the microenvironment of follicular growth may be reflected by microRNA (miRNA) expression profiles. Downregulation of miR-4261 when progesterone is added in the follicular phase has been reported in our previous research. The purpose of this study is to observe how miR-4261 regulates the function of granulosa cells, so as to find the specific pathway and mechanism of progesterone acting on the follicular microenvironment. Results: The human ovarian granulosa cell line (KGN cells) is used to conduct cell experiments as granulosa cells. Compared with microRNA-negative control (miR-NC), KGN cells transfected with the miR-4261 mimic showed progressively reduced proliferation at 24, 48, and 72 h (p < 0.01). The levels of Frizzled 5 (FZD5) mRNA and protein were also significantly reduced (p < 0.01). In the dual-luciferase reporter gene experiment, the fluorescence value of KGN cells co-transfected with wild type-FZD5 (wt-FZD5) and the miR-4261 mimic/inhibitor decreased/increased (p < 0.01), and there was no significant difference in fluorescence value between mutant-FZD5 (mut-FZD5) and the miR-4261 mimic/inhibitor co-transfected KGN cells (p > 0.05). The proliferation activity of KGN cells transfected with small interfering FZD5 (siFZD5) decreased significantly at 48 h (p < 0.01) compared with the control. Compared with KGN cells co-transfected with siFZD5 and miR-NC, there was no significant difference in the proliferation activity of KGN cells co-transfected with siFZD5 and miR-4261 inhibitor (p > 0.05). Conclusions: The down-regulation of miR-4261 can promote the proliferation of granulosa cells. The knockdown of FZD5 can inhibit the proliferation of granulosa cells. FZD5 is the direct downstream target gene of miR-4261 in KGN cells. miR-4261 can regulate granulosa cell proliferation by targeting FZD5.
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BibTeX
@article{yu2026mir4261,
title = {{MiR-4261 Regulates Granulosa Cell Proliferation Mediated by Progesterone via FZD5 in Human Ovarian Granulosa Cell Line.}},
author = {Jiao Yu and Yangyang Zhang and Yanrong Kuai and Sheng Wang and Yang Xu},
journal = {Genes},
year = {2026},
month = oct,
doi = {10.3390/genes17101297},
url = {https://europepmc.org/article/MED/42938413},
note = {CC BY},
}
RIS
TY - JOUR
TI - MiR-4261 Regulates Granulosa Cell Proliferation Mediated by Progesterone via FZD5 in Human Ovarian Granulosa Cell Line.
AU - Jiao Yu
AU - Yangyang Zhang
AU - Yanrong Kuai
AU - Sheng Wang
AU - Yang Xu
PY - 2026
DA - 2026/10/18
JO - Genes
DO - 10.3390/genes17101297
UR - https://europepmc.org/article/MED/42938413
AB - Background: The effect of different controlled ovarian hyperstimulation (COH) protocols on the microenvironment of follicular growth may be reflected by microRNA (miRNA) expression profiles. Downregulation of miR-4261 when progesterone is added in the follicular phase has been reported in our previous research. The purpose of this study is to observe how miR-4261 regulates the function of granulosa cells, so as to find the specific pathway and mechanism of progesterone acting on the follicular microenvironment. Results: The human ovarian granulosa cell line (KGN cells) is used to conduct cell experiments as granulosa cells. Compared with microRNA-negative control (miR-NC), KGN cells transfected with the miR-4261 mimic showed progressively reduced proliferation at 24, 48, and 72 h (p < 0.01). The levels of Frizzled 5 (FZD5) mRNA and protein were also significantly reduced (p < 0.01). In the dual-luciferase reporter gene experiment, the fluorescence value of KGN cells co-transfected with wild type-FZD5 (wt-FZD5) and the miR-4261 mimic/inhibitor decreased/increased (p < 0.01), and there was no significant difference in fluorescence value between mutant-FZD5 (mut-FZD5) and the miR-4261 mimic/inhibitor co-transfected KGN cells (p > 0.05). The proliferation activity of KGN cells transfected with small interfering FZD5 (siFZD5) decreased significantly at 48 h (p < 0.01) compared with the control. Compared with KGN cells co-transfected with siFZD5 and miR-NC, there was no significant difference in the proliferation activity of KGN cells co-transfected with siFZD5 and miR-4261 inhibitor (p > 0.05). Conclusions: The down-regulation of miR-4261 can promote the proliferation of granulosa cells. The knockdown of FZD5 can inhibit the proliferation of granulosa cells. FZD5 is the direct downstream target gene of miR-4261 in KGN cells. miR-4261 can regulate granulosa cell proliferation by targeting FZD5.
SN - 2073-4425
ER -