LncRNA MALAT1 inhibits apoptosis of endometrial stromal cells through miR-126-5p-CREB1 axis by activating PI3K-AKT pathw
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LncRNA MALAT1 inhibits apoptosis of endometrial stromal cells through miR‑126‑5p‑CREB1 axis by activating PI3K‑AKT pathway Ying Feng1 · Bu‑Zhen Tan1 Received: 30 March 2020 / Accepted: 1 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Endometriosis · Apoptosis · lncRNA MALAT1 · miR-126-5p · CREB1 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
* Bu‑Zhen Tan [email protected] 1
Department of Obstetrics and Gynecology, Donghu District, the Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang 330006, Jiangxi Province, China
Introduction Endometriosis is a common benign disease and has similar biological features to malignant tumor, including malignant proliferation, apoptosis inhibition, invasiveness, easy to recurrence and malignant transformation, etc. [1, 2]. Endometriosis means that the endometrial glands and stroma infiltrate in other place outside the uterus. The morbidity of endometriosis is 10–15% in bearing aged women, and 20–40% in sterility women [3]. This disease may cause dysmenorrhea, chronic pelvic pain, or infertility, which not only impairs life quality of patients, but also aggravates their psychology burden. However, the pathoge
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