LncRNA MALAT1 inhibits apoptosis of endometrial stromal cells through miR-126-5p-CREB1 axis by activating PI3K-AKT pathway

Endometriosis is a common, chronic and painful disease in women, whose pathogenesis remains not entirely clear. Long non-coding RNA (lncRNA) MALAT1 participates in the development of endometriosis. This study further investigated the regulation of MALAT1-miR-126-5p-CREB1 axis in the pathological process of endometriosis. MALAT1, miR-126-5p, and CREB1 levels in human endometrial stromal cells (HESCs) were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Protein levels were determined by Western blotting. Cell viability and apoptosis was assessed by MTT assay and annexin V-FITC staining, respectively. The interactivity between miR-126-5p and MALAT1 (or CREB1) was assessed by dual luciferase reporter system. Knockdown of MALAT1 or CREB1 restrained proliferation and induced apoptosis as confirmed by upregulating cleaved caspase-3 and Bax, and down-regulating Bcl-2 in HESCs, while inhibition of miR-126-5p presented the opposite results. Moreover, silencing of MALAT1 triggered apoptosis of HESCs via targeting miR-126-5p. In addition, miR-126-5p directly regulated CREB1 expression via binding to its 3′ non-coding region. Finally, miR-126-5p inhibitor-mediated apoptosis inhibition was restrained by CREB1 silencing via inactivation of PI3K-AKT pathway in HESCs. Taken together, our study firstly demonstrates that MALAT1 regulates apoptosis of HESCs through miR-126-5p/CREB1 axis mediated PI3K/AKT pathway. Our findings explained the pathogenesis of endometriosis and offered promising therapeutic option for endometriosis. Similar content being viewed by others Abbreviations - HESCs: - Human endometrial stromal cells - lncRNAs: - Long non-coding RNAs - miRNA: - MicroRNA - CREB1: - Cyclic AMP response element-binding protein 1 - DMSO: - Dimethylsulfoxide - WT: - Wild type - MUT: - Mutant - UTR: - Untranslated regions - RT-qPCR: - Quantitative reverse transcription polymerase chain reaction

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Material preparation, data collection and analysis were performed by YF and B-ZT. The first draft of the manuscript was written by YF and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Ethics approval The experiment was carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards, and approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University. Informed consent All patients signed written informed consent. The informed consent was obtained from study participants. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Feng, Y., Tan, BZ. LncRNA MALAT1 inhibits apoptosis of endometrial stromal cells through miR-126-5p-CREB1 axis by activating PI3K-AKT pathway. Mol Cell Biochem 475, 185–194 (2020). https://doi.org/10.1007/s11010-020-03871-y Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11010-020-03871-y