Downregulation of lncRNA XIST promotes proliferation and differentiation, limits apoptosis of osteoblasts through regulating miR-203-3p/ZFPM2 axis

Niu, Shizhen; Feng, Xin; Jia, Huaihai

doi:10.1080/03008207.2020.1752200

Cited by 11 publications

(10 citation statements)

References 34 publications

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“…They are usually genetically modified to participate in the mediation of bone formation. Over the last decade, accumulating evidences have shown that lncRNAs play diversity roles on cell proliferation, migration, and osteoblasts differentiation [ 32 , 33 ]. Taking the diverse regulatory modes and biological functions of lncRNAs on bone homeostasis into account, it has become the research hotspot.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of lncRNA-miRNA-mRNA networks during osteogenic differentiation of bone marrow mesenchymal stem cells

et al. 2022

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Background Long non-coding RNA (lncRNA) plays crucial role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), involving in regulation of competing endogenous RNA (ceRNA) mechanisms and conduction of signaling pathways. However, its mechanisms are poorly understood. This study aimed to investigate lncRNAs, miRNAs and mRNAs expression profiles in rat BMMSCs (rBMMSCs) osteogenic differentiation, screen the potential key lncRNA-miRNA-mRNA networks, explore the putative functions and identify the key molecules, as the basis of studying potential mechanism of rBMMSCs osteogenic differentiation driven by lncRNA, providing molecular targets for the management of bone defect. Methods High-throughput RNA sequencing (RNA-seq) was used to determine lncRNAs, miRNAs, and mRNAs expression profiles at 14-day rBMMSCs osteogenesis. The pivotal lncRNA-miRNA and miRNA-mRNA networks were predicted from sequencing data and bioinformatic analysis, and the results were exported by Cytoscape 3.9.0 software. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used for functional exploration. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate lncRNAs, miRNAs and mRNAs. Results rBMMSCs were identified, and the osteogenic and adipogenic differentiation ability were detected. A total of 8634 lncRNAs were detected by RNA-seq, and 1524 differential expressed lncRNAs, of which 812 up-regulated and 712 down-regulated in osteo-inductive groups compared with control groups. 30 up-regulated and 61 down-regulated miRNAs, 91 miRNAs were differentially expressed in total. 2453 differentially expressed mRNAs including 1272 up-expressed and 1181 down-expressed were detected. 10 up-regulated lncRNAs were chosen to predict 21 down-regulated miRNAs and 650 up-regulated mRNAs. 49 lncRNA-miRNA and 1515 miRNA–mRNA interactive networks were constructed. GO analysis showed the most important enrichment in cell component and molecular function were “cytoplasm” and “protein binding”, respectively. Biological process related to osteogenic differentiation such as “cell proliferation”, “wound healing”, “cell migration”, “osteoblast differentiation”, “extracellular matrix organization” and “response to hypoxia” were enriched. KEGG analysis showed differentially expressed genes were mainly enriched in “PI3K-Akt signaling pathway”, “Signaling pathway regulating pluripotency of stem cells”, “cGMP-PKG signaling pathway”, “Axon guidance” and “Calcium signaling pathway”. qRT-PCR verified that lncRNA Tug1, lncRNA AABR07011996.1, rno-miR-93-5p, rno-miR-322-5p, Sgk1 and Fzd4 were consistent with the sequencing results, and 4 lncRNA-miRNA-mRNA networks based on validations were constructed, and enrichment pathways were closely related to “PI3K-Akt signaling pathway”, “Signaling pathway regulating pluripotency of stem cells” and “Wnt signaling pathway”. Conclusions lncRNAs, miRNAs and mRNAs expression profiles provide clues for future studies on their roles for BMMSCs osteogenic differentiation. Furthermore, lncRNA–miRNA–mRNA networks give more information on potential new mechanisms and targets for management on bone defect.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of lncRNA-miRNA-mRNA networks during osteogenic differentiation of bone marrow mesenchymal stem cells

et al. 2022

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“…Furthermore, knockdown of XiST can suppress oB apoptosis induced by ia via the regulation of caspase 3. Similarly, niu et al (121) revealed that XiST, which was found to be upregulated in plasma, also promoted oB apoptosis through the mir-203-3p/ZFPM2 pathway. in addition, XiST plays a role in regulating oB differentiation by modulating the expression of mir-19a-3p, indicating that XiST performs various important regulatory functions in bone-related diseases (12).…”

Section: Effects Of Lncrnas On Regulation Of Obsmentioning

confidence: 91%

Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review)

Han

Tan

et al. 2021

Mol Med Rep

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osteoporosis is a common metabolic bone disorder typically characterized by decreased bone mass and an increased risk of fracture. at present, the detailed molecular mechanism underlying the development of osteoporosis remains to be elucidated. accumulating evidence shows that non-coding (nc)rnas, such as micrornas (mirnas), long ncrnas (lncrnas) and circular rnas (circRNAs), play significant roles in osteoporosis through the post-transcriptional regulation of gene expression as regulatory factors. Previous studies have demonstrated that ncrnas participate in maintaining bone homeostasis by regulating physiological and developmental processes in osteoblasts, osteoclasts and bone marrow stromal cells. in the present review, the latest research investigating the involvement of mirnas, lncrnas and circrnas in regulating the differentiation, proliferation, apoptosis and autophagy of cells that maintain the bone microenvironment in osteoporosis is summarized. deeper insight into the aspects of osteoporosis pathogenesis involving the deregulation of ncrnas could facilitate the development of therapeutic approaches for osteoporosis. Contents 1. introduction 2. Mechanisms by which ncrnas regulate BMScs in osteoporosis 3. Mechanisms by which ncrnas regulate oBs in osteoporosis 4. Mechanisms by which ncrnas regulate ocs in osteoporosis 5. conclusion and perspectives

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“…In polycystic ovary syndrome (PCOS), lncRNA Xist is correlated with adverse pregnancy outcomes ( Liu et al, 2020c ). In addition, these signaling pathways, which include lncRNA Xist/miR-203-3p/ZFPM2 ( Niu et al, 2020 ), lncRNA Xist/let-7c-5p/STAT3 ( Wang et al, 2020d ), and lncRNA Xist/miR-320/NOD2 ( Xu X.H. et al, 2018 ), have been identified as a ceRNA regulatory network and participated in osteoblast development and ox-LDL (oxidative low-density lipoprotein)-induced endothelial cells injury.…”

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.

124

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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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Downregulation of lncRNA XIST promotes proliferation and differentiation, limits apoptosis of osteoblasts through regulating miR-203-3p/ZFPM2 axis

Cited by 11 publications

References 34 publications

Comprehensive analysis of lncRNA-miRNA-mRNA networks during osteogenic differentiation of bone marrow mesenchymal stem cells

Comprehensive analysis of lncRNA-miRNA-mRNA networks during osteogenic differentiation of bone marrow mesenchymal stem cells

Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review)

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

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