Long noncoding RNA XIST regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting miR-9-5p

Zheng, Chenying; Bai, Chunxiao; Sun, Qi; Zhang, Fan; Yu, Qinsheng; Zhao, Xueqian; Kang, Shengqian; Li, Jinyu; Jia, Yu-Song

doi:10.1016/j.mod.2020.103612

Cited by 24 publications

(21 citation statements)

References 38 publications

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“…The result showed that 13 miRNAs were remarkably highly expressed in PBMC of mice with osteoporosis. Among the 13 miRNAs, the expression trends of miR-1271-5p, miR-135a-5p, miR-135b-5p, miR-153-3p, miR-223-3p, miR-27a-3p, miR-370-3p, and miR-9-5p in the current study were in line with their trends in various studies [ 5 , 7 , 41 – 46 ]. Our result revealed that the expression of the 13 miRNAs was positively correlated with the progression of osteoporosis.…”

Section: Discussionsupporting

confidence: 88%

Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches

Lü

Wang

Xue

et al. 2021

Computational and Mathematical Methods in Medicine

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Osteoporosis is a degenerative osteoarthropathy commonly found in old people and postmenopausal women. Many studies showed that microRNAs (miRNAs) can regulate the expression of osteoporosis-related genes and are abnormally expressed in patients with osteoporosis. miRNAs therefore have the potential to serve as biomarkers of osteoporosis. In this study, the limma package was used for the differential expression analysis of mRNA expression profiles and 357 significantly differentially expressed genes (DEGs) were obtained. Metascape was used for functional enrichment analysis of DEGs. The result revealed that DEGs were mainly enriched in signaling pathways like MAPK6/MAPK4. Based on the STRING database, the protein-protein interaction (PPI) network of DEGs was constructed. MCODE was used to analyze the functional subsets, and a key functional subset composed of 9 genes was screened out. In addition, the miRNA-mRNA regulatory interaction network (RegIN) was analyzed by the CyTargetLinker plugin, which generated 55 miRNA-mRNA regulatory interactions. Through literature searching, the osteoporosis-related gene FOXO1 in the key functional subset was determined to be the main object of the study. In qRT-PCR assay, the expression of the predicted miRNAs was tested in peripheral blood mononuclear cells of mice with osteoporosis, in which 13 miRNAs were remarkably highly expressed. All in all, this study, based on bioinformatics analysis and testing assay of miRNA expression, determined the potential biomarkers of osteoporosis.

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Section: Discussionsupporting

confidence: 88%

Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches

Lü

Wang

Xue

et al. 2021

Computational and Mathematical Methods in Medicine

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“…Jia et al found that the expression of miR-9-5p was downregulated in human bone marrow mesenchymal stem cells (hBMSCs) from osteoporotic patients and con rmed that miR-9-5p inhibited the osteogenic differentiation of hBMSCs. 23 Lu et al found that miR-9-5p reduced skeletal cell count and cell proliferation and impaired osteoblasts differentiation. Furthermore, they also con rmed that miR-9-5p impaired bone formation through induction of osteoblasts apoptosis.…”

Section: Discussionmentioning

confidence: 99%

CircStrn3 Targeting microRNA-9-5p is Involved in the Regulation of Cartilage Degeneration and Subchondral Bone Remodeling in Osteoarthritis

Ding

Chen

et al. 2021

SSRN Journal

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Background: Osteoarthritis (OA) is the most frequent chronic degenerative joint disease, which is a "whole joint" disease including the pathological changes in the cartilage, subchondral bone and the synovium. Mechanical instability is the initiation of the development of OA.Methods: Minus RNA sequencing, uorescence in situ hybridization and quantitative real-time PCR were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes.Stimulate chondrocytes to secrete exosomes miR-9-5p by stretching strain. Intra-articular injection of exosomes miR-9-5p into the OA model induced by the operation of instability of the medial meniscus in mice.Results: In the present study, minus RNA sequencing data showed that tensile strain could decrease the expression of circStrn3 in chondrocytes. The results of uorescence in situ hybridization and quantitative Real-time PCR showed that circStrn3 expression was signi cantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively 'sponging' miRNA-9-5p targeting kruppel-like factor 5 (KLF5), indicating that the decreasing of circStrn3 might be a protective factor in mechanical instability-induced OA. Further studies showed that the tensile strain stimulated chondrocytes to secrete exosomes miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblasts differentiation by targeting KLF5. In addition, intra-articular injection of exosomal miR-9-5p obviously alleviated the progression of OA induced by destabilized medial meniscus surgery in mice.Conclusions: Taken together, these results demonstrated that the reduction of circStrn3 caused the increasing of miR-9-5p, which acted as a protective factor in mechanical instability-induced OA and provided a novel mechanism of communication among joint components and a potential application for the treatment of OA.

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“…Trisomy 21, Pitx3, TLR5, TNFAIP1, STAT3, ZEB1 Jin et al, 2018;Yan et al, 2018;Wei et al, 2019 Neurodegeneration miR-133b-3p Pitx3 He et al, 2020 Alzheimer's disease miR-132, miR-124 BACE1 Wang et al, 2018b;Du Y. et al, 2020Osteoarthritis miR-211, miR-214-3p, miR-17-5p, miR-1277 CXCR4, MAPK, AHNAK, BMP2, TIMP-3, MMP-13, ADAMTS5, OPN, SGTB, DNMT3A, GNG5 Liao et al, 2019;Wang et al, 2019e;Feng et al, 2020;Ghaderian et al, 2020;Li et al, 2020b;Liu et al, 2020e;Shen X.F. et al, 2020 Bone marrow miR-9-5p ALPL, ALP, Bglap, Runx2 Zheng C. et al, 2020 Inflammation miR-27a-3p, miR-34a, miR-30c-5p, miR-146a NF−κB, NLRP3, Smurf1, YY1, PTEN, Nav1.7 Shenoda et al, 2018;Sun W.B. et al, 2018;Hu W.N.…”

Section: Lncrna Xist In Neuropathic Painmentioning

confidence: 99%

“…In addition, a major role of lncRNA Xist is facilitating gene expression and affecting osteoarthritis development and progression via sponging to miRNAs. The lncRNA Xist/miR-9-5p/ALPL ( Zheng C. et al, 2020 ) and lncRNA Xist/miR-1277-5p/MMP-13 and ADAMTS5 ( Wang et al, 2019e ) signaling pathway has been identified as a ceRNA regulatory network involved in osteoarthritis development. And other ceRNA regulatory networks have also been shown to contribute to the progression of Osteoarthritis, such as lncRNA Xist/miR-376c-5p/OPN signaling pathway ( Li et al, 2020b ), lncRNA Xist/miR-142-5p/SGTB signaling pathway ( Ghaderian et al, 2020 ), lncRNA Xist/miR-149-5p/DNMT3A signaling pathway ( Liu et al, 2020e ), and lncRNA Xist/miR-675-3p/GNG5 signaling pathway ( Shen X.F.…”

Section: The Role Of Lncrna Xist In Non-cancer Diseasesmentioning

confidence: 99%

Biological Function of Long Non-coding RNA (LncRNA) Xist

Wang

Min

Guo

et al. 2021

Front. Cell Dev. Biol.

125

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Long non-coding RNAs (lncRNAs) regulate gene expression in a variety of ways at epigenetic, chromatin remodeling, transcriptional, and translational levels. Accumulating evidence suggests that lncRNA X-inactive specific transcript (lncRNA Xist) serves as an important regulator of cell growth and development. Despites its original roles in X-chromosome dosage compensation, lncRNA Xist also participates in the development of tumor and other human diseases by functioning as a competing endogenous RNA (ceRNA). In this review, we comprehensively summarized recent progress in understanding the cellular functions of lncRNA Xist in mammalian cells and discussed current knowledge regarding the ceRNA network of lncRNA Xist in various diseases. Long non-coding RNAs (lncRNAs) are transcripts that are more than 200 nt in length and without an apparent protein-coding capacity (Furlan and Rougeulle, 2016; Maduro et al., 2016). These RNAs are believed to be transcribed by the approximately 98–99% non-coding regions of the human genome (Derrien et al., 2012; Fu, 2014; Montalbano et al., 2017; Slack and Chinnaiyan, 2019), as well as a large variety of genomic regions, such as exonic, tronic, and intergenic regions. Hence, lncRNAs are also divided into eight categories: Intergenic lncRNAs, Intronic lncRNAs, Enhancer lncRNAs, Promoter lncRNAs, Natural antisense/sense lncRNAs, Small nucleolar RNA-ended lncRNAs (sno-lncRNAs), Bidirectional lncRNAs, and non-poly(A) lncRNAs (Ma et al., 2013; Devaux et al., 2015; St Laurent et al., 2015; Chen, 2016; Quinn and Chang, 2016; Richard and Eichhorn, 2018; Connerty et al., 2020). A range of evidence has suggested that lncRNAs function as key regulators in crucial cellular functions, including proliferation, differentiation, apoptosis, migration, and invasion, by regulating the expression level of target genes via epigenomic, transcriptional, or post-transcriptional approaches (Cao et al., 2018). Moreover, lncRNAs detected in body fluids were also believed to serve as potential biomarkers for the diagnosis, prognosis, and monitoring of disease progression, and act as novel and potential drug targets for therapeutic exploitation in human disease (Jiang W. et al., 2018; Zhou et al., 2019a). Long non-coding RNA X-inactive specific transcript (lncRNA Xist) are a set of 15,000–20,000 nt sequences localized in the X chromosome inactivation center (XIC) of chromosome Xq13.2 (Brown et al., 1992; Debrand et al., 1998; Kay, 1998; Lee et al., 2013; da Rocha and Heard, 2017; Yang Z. et al., 2018; Brockdorff, 2019). Previous studies have indicated that lncRNA Xist regulate X chromosome inactivation (XCI), resulting in the inheritable silencing of one of the X-chromosomes during female cell development. Also, it serves a vital regulatory function in the whole spectrum of human disease (notably cancer) and can be used as a novel diagnostic and prognostic biomarker and as a potential therapeutic target for human disease in the clinic (Liu et al., 2018b; Deng et al., 2019; Dinescu et al., 2019; Mutzel and Schulz, 2020; Patrat et al., 2020; Wang et al., 2020a). In particular, lncRNA Xist have been demonstrated to be involved in the development of multiple types of tumors including brain tumor, Leukemia, lung cancer, breast cancer, and liver cancer, with the prominent examples outlined in Table 1. It was also believed that lncRNA Xist (Chaligne and Heard, 2014; Yang Z. et al., 2018) contributed to other diseases, such as pulmonary fibrosis, inflammation, neuropathic pain, cardiomyocyte hypertrophy, and osteoarthritis chondrocytes, and more specific details can be found in Table 2. This review summarizes the current knowledge on the regulatory mechanisms of lncRNA Xist on both chromosome dosage compensation and pathogenesis (especially cancer) processes, with a focus on the regulatory network of lncRNA Xist in human disease.

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Long noncoding RNA XIST regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting miR-9-5p

Cited by 24 publications

References 38 publications

Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches

Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches

CircStrn3 Targeting microRNA-9-5p is Involved in the Regulation of Cartilage Degeneration and Subchondral Bone Remodeling in Osteoarthritis

Biological Function of Long Non-coding RNA (LncRNA) Xist

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