Downregulating lncRNA NEAT1 induces proliferation and represses apoptosis of ovarian granulosa cells in polycystic ovary syndrome via microRNA-381/IGF1 axis
Authors: Zhengyi Sun
Yaling Xiao
Qi Yu
Xue Wang
Jiangli Li
Jingran Zhen
Xia Li
Journal: Journal of Biomedical Science (2021)
Discipline: CLINICAL MEDICINE
Keywords: Apoptosis; Insulin-like growth factor 1; Long non-coding RNA nuclear-enriched abundant transcript 1; MicroRNA-381; Ovarian granulosa cells
Affiliations: Department of Gynecological Endocrinology and Reproduction Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 41 Damucang Hutong, Xicheng, Beijing, China., Department of Obstetrics and Gynecology, Zhongguancun Hospital, Beijing, 100080, China., Community Health Service Center, Beijing Forestry University, Beijing, 100053, China., Department of Gynecological Endocrinology and Reproduction Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 41 Damucang Hutong, Xicheng, Beijing, China. .

Abstract:  Objective: Researchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS. Methods: PCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro. Results: NEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis. Conclusion: Interference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS. 

Retracted: Yes

PubPeer comments:
 Figs 1D, 2I, 5C, 6D. ![file] Is it possible for the authors to upload scans of the original gels for these eyebrow-like Western Blots? They sample the same confined region of morphology space as Figs 1b, 7a of [Yang et al (2021)] ... ![] ... and Figs 5b,d and 7b from [Tang Hu (2021)] . ![] Another feature that is common to these papers is an Acknowledgement,  We would like to acknowledge the reviewers for their helpful comments on this paper . This would be unexceptional on its own, but when combined with several other common features, it is suggestive of a common source. , 
 This article shares several characteristics with others in the eyebrow family of papers identified by Hoya Camphorifolia. 1. Table 2 is  Primer sequence (Table 1 in most examined papers in this group) 2. Primer problems: Investigated miRNA is miR-381-3p (Fig2A,D), but miRNA forward primer is miR-381-5p, and only 11 nt. The 5 nucleotides would bind to the miR-381 precursor, but these nts should not be present on the mature miRNA. Unclear what the reverse primer is; it binds 18 nt stretch in human SIDT2. 3. miRNA RT: No miRNA-specific RT method. Mature miRNA could not have been amplified. 4. miRNA normalizer: Not specified in methods , 
  14 September 2021 Editoru2019s Note: Readers are alerted that the reliability of data presented in this manuscript is currently in question. Appropriate editorial action will be taken once this matter is resolved. , 
 Retracted [30 March 2022] . ------------------------------- The Editor-in-Chief has retracted this Article. Concerns were raised about the authenticity of the western blot data. The Authors were unable to provide uncropped images of the original gels. Additionally, there are fundamental flaws in the flow cytometry apoptosis assay methodology. The Editor-in-Chief therefore no longer has confidence in the data and conclusions of this study. Zhengyi Sun agrees to this retraction. Jingran Zhen has not explicitly stated whether they agree to this retraction notice. Qi Yu does not agree to this retraction. Jiangli Li, Xia Li, Xue Wang and Yaling Xiao have not responded to any correspondence from the editor about this retraction. ,