miR-141-3p Regulates the Proliferation and Apoptosis of Endometrial-Myometrial Interface Smooth Muscle Cells in Adenomyosis Via JAK2/STAT3 Pathway

Adenomyosis (ADS) is a common benign gynecological disease. Abnormal proliferation at the endometrial-myometrial interface (EMI) plays a crucial role in the occurrence and progression of ADS. miR-141-3p is associated with cell proliferation and apoptosis. However, the specific mechanism of miR-141-3p in the etiology of ADS is still unknown. In this study, we explored the effects of miR-141-3p on the proliferation and apoptosis of ADS EMI smooth muscle cells (SMCs). We collected EMI tissues for the primary culture of SMCs from 25 patients diagnosed with ADS and 20 without ADS. Real-time quantitative polymerase chain reaction and western blot were used to measure the mRNA and protein expression levels of miR-141-3p, JAK2, STAT3, phospho-JAK2, and phospho-STAT3 in ADS EMI SMCs. The cell counting kit 8 assay and flow cytometry analysis were used to evaluate the proliferation and apoptosis of EMI SMCs. The miR-141-3p mimic/inhibitor was used to increase or decrease the expression level of miR-141-3p. We added WP1066 to block the phosphorylation of JAK2/STAT3 pathway components. The miR-141-3p levels were decreased, while JAK2 and STAT3 levels were increased in ADS EMI SMCs. miR-141-3p overexpression significantly inhibited the proliferation and enhanced the apoptosis of EMI SMCs, whereas a decrease in miR-141-3p expression level was connected to the opposite results. Meanwhile, inactivated JAK2/STAT3 pathway decreased proliferation and enhanced apoptosis of EMI SMCs after WP1066 treatment. Furthermore, rescue experiments confirmed that the JAK2/STAT3 pathway was the downstream pathway of miR-141-3p and reduced the effect of miR-141-3p on the proliferation and apoptosis of EMI SMCs. These results demonstrate that miR-141-3p regulates the proliferation and apoptosis of ADS EMI SMCs by modulating the JAK2/STAT3 pathway. Similar content being viewed by others Data Availability Supporting and raw data are available upon a reasonable request to the corresponding author. Abbreviations - ADS: - adenomyosis - EMI: - endometrial-myometrial interface - SMCs: - smooth muscle cells - JAK2: - The Janus Kinase2 - STAT3: - signal transducer and activator of transcription3 - p-JAK2: - phosphorylated The Janus Kinase2 - p-STAT3: - phosphorylated signal transducer and activator of transcription3 - α-SMA: - alpha-smooth muscle actin - RT-qPCR: - real-time quantitative polymerase chain reaction - CCK-8: - cell counting kit-8

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We would like to thank to Medical Research Center, Beijing Chao-Yang Hospital for providing us with the experimental platform. Funding This study was funded by National Natural Science Foundation of China (No. 81571412). Author information Authors and Affiliations Contributions Sirui Wang drafted the manuscript, completed all the experiments and analyzed the data of the study. Hua Duan participated in the study design and revised the manuscript. Sha Wang helped to analyze the experimental data. Zhengchen Guo and Qi Lin helped with collection of tissue samples and acquisition of data. All authors approved the final version of the manuscript. Corresponding author Ethics declarations Ethics Approval and Consent to Participate This study was authorized by the Ethics Committee of our hospital (No. 2016-KY-012-02). All patients signed an informed consent form before the hysterectomy. Consent for Publication Not applicable. Competing Interests The authors declare that they have no known competing interests that could have appeared to influence the work reported in this paper. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Wang, S., Duan, H., Wang, S. et al. miR-141-3p Regulates the Proliferation and Apoptosis of Endometrial-Myometrial Interface Smooth Muscle Cells in Adenomyosis Via JAK2/STAT3 Pathway. Biochem Genet 62, 2049–2065 (2024). https://doi.org/10.1007/s10528-023-10508-4 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10528-023-10508-4