Long noncoding RNA XIST: Mechanisms for X chromosome inactivation, roles in sex-biased diseases, and therapeutic opportunities

Genes and Diseases - Tập 9 - Trang 1478-1492 - 2022
Jianjian Li1, Zhe Ming1, Liuyi Yang1, Tingxuan Wang1, Gaowen Liu1, Qing Ma1
1Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, PR China

Tài liệu tham khảo

Mercer, 2009, Long non-coding RNAs: insights into functions, Nat Rev Genet, 10, 155, 10.1038/nrg2521 Gil, 2020, Regulation of gene expression by cis-acting long non-coding RNAs, Nat Rev Genet, 21, 102, 10.1038/s41576-019-0184-5 Quinodoz, 2021, RNA promotes the formation of spatial compartments in the nucleus, Cell, 184, 5775, 10.1016/j.cell.2021.10.014 Razin, 2021, Non-coding RNAs in chromatin folding and nuclear organization, Cell Mol Life Sci, 78, 5489, 10.1007/s00018-021-03876-w Tachiwana, 2020, Gene regulation by non-coding RNAs in the 3D genome architecture, Curr Opin Genet Dev, 61, 69, 10.1016/j.gde.2020.03.002 Wang, 2021, The role of long non-coding RNAs in human imprinting disorders: prospective therapeutic targets, Front Cell Dev Biol, 9, 730014, 10.3389/fcell.2021.730014 Fatica, 2014, Long non-coding RNAs: new players in cell differentiation and development, Nat Rev Genet, 15, 7, 10.1038/nrg3606 Bhan, 2017, Long noncoding RNA and cancer: a new paradigm, Cancer Res, 77, 3965, 10.1158/0008-5472.CAN-16-2634 Batista, 2013, Long noncoding RNAs: cellular address codes in development and disease, Cell, 152, 1298, 10.1016/j.cell.2013.02.012 Penny, 1996, Requirement for Xist in X chromosome inactivation, Nature, 379, 131, 10.1038/379131a0 Okamoto, 2021, The X chromosome dosage compensation program during the development of cynomolgus monkeys, Science, 374, 10.1126/science.abd8887 Yu, 2021, B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells, Cell, 184, 1790, 10.1016/j.cell.2021.02.015 Deng, 2014, X chromosome regulation: diverse patterns in development, tissues and disease, Nat Rev Genet, 15, 367, 10.1038/nrg3687 Schulz, 2013, Role and control of X chromosome dosage in mammalian development, Curr Opin Genet Dev, 23, 109, 10.1016/j.gde.2013.01.008 Patrat, 2020, X chromosome inactivation in human development, Development, 147, dev183095, 10.1242/dev.183095 Okamoto, 2011, Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development, Nature, 472, 370, 10.1038/nature09872 Sahakyan, 2018, The role of Xist in X-chromosome dosage compensation, Trends Cell Biol, 28, 999, 10.1016/j.tcb.2018.05.005 Sidorenko, 2019, The effect of X-linked dosage compensation on complex trait variation, Nat Commun, 10, 3009, 10.1038/s41467-019-10598-y Maduro, 2016, Fitting the puzzle pieces: the bigger picture of XCI, Trends Biochem Sci, 41, 138, 10.1016/j.tibs.2015.12.003 Brown, 1992, The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus, Cell, 71, 527, 10.1016/0092-8674(92)90520-M Brown, 1991, A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome, Nature, 349, 38, 10.1038/349038a0 Brockdorff, 1991, Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome, Nature, 351, 329, 10.1038/351329a0 Markaki, 2021, Xist nucleates local protein gradients to propagate silencing across the X chromosome, Cell, 184, 6174, 10.1016/j.cell.2021.10.022 Żylicz, 2019, The implication of early chromatin changes in X chromosome inactivation, Cell, 176, 182, 10.1016/j.cell.2018.11.041 Xu, 2006, Transient homologous chromosome pairing marks the onset of X inactivation, Science, 311, 1149, 10.1126/science.1122984 Monkhorst, 2008, X inactivation counting and choice is a stochastic process: evidence for involvement of an X-linked activator, Cell, 132, 410, 10.1016/j.cell.2007.12.036 Jégu, 2017, The X chromosome in space, Nat Rev Genet, 18, 377, 10.1038/nrg.2017.17 Furlan, 2018, The ftx noncoding locus controls X chromosome inactivation independently of its RNA products, Mol Cell, 70, 462, 10.1016/j.molcel.2018.03.024 Tian, 2010, The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation, Cell, 143, 390, 10.1016/j.cell.2010.09.049 Sun, 2013, Jpx RNA activates xist by evicting CTCF, Cell, 153, 1537, 10.1016/j.cell.2013.05.028 Jonkers, 2009, RNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation, Cell, 139, 999, 10.1016/j.cell.2009.10.034 Lee, 1999, Tsix, a gene antisense to Xist at the X-inactivation centre, Nat Genet, 21, 400, 10.1038/7734 Lee, 2005, Regulation of X-chromosome counting by Tsix and Xite sequences, Science, 309, 768, 10.1126/science.1113673 Bell, 1999, The protein CTCF is required for the enhancer blocking activity of vertebrate insulators, Cell, 98, 387, 10.1016/S0092-8674(00)81967-4 Navarro, 2006, Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program, Genes Dev, 20, 2787, 10.1101/gad.389006 Gontan, 2012, RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation, Nature, 485, 386, 10.1038/nature11070 Navarro, 2010, Molecular coupling of Tsix regulation and pluripotency, Nature, 468, 457, 10.1038/nature09496 Makhlouf, 2014, A prominent and conserved role for YY1 in Xist transcriptional activation, Nat Commun, 5, 4878, 10.1038/ncomms5878 Robert-Finestra, 2021, SPEN is required for Xist upregulation during initiation of X chromosome inactivation, Nat Commun, 12, 7000, 10.1038/s41467-021-27294-5 Fukuda, 2021, De novo DNA methyltransferases DNMT3A and DNMT3B are essential for XIST silencing for erosion of dosage compensation in pluripotent stem cells, Stem Cell Reports, 16, 2138, 10.1016/j.stemcr.2021.07.015 Chu, 2015, Systematic discovery of Xist RNA binding proteins, Cell, 161, 404, 10.1016/j.cell.2015.03.025 Grant, 1992, Methylation of CpG sites of two X-linked genes coincides with X-inactivation in the female mouse embryo but not in the germ line, Nat Genet, 2, 161, 10.1038/ng1092-161 Jeppesen, 1993, The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression, Cell, 74, 281, 10.1016/0092-8674(93)90419-Q Chaumeil, 2002, Integrated kinetics of X chromosome inactivation in differentiating embryonic stem cells, Cytogenet Genome Res, 99, 75, 10.1159/000071577 Heard, 2001, Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation, Cell, 107, 727, 10.1016/S0092-8674(01)00598-0 Keniry, 2016, Setdb1-mediated H3K9 methylation is enriched on the inactive X and plays a role in its epigenetic silencing, Epigenetics Chromatin, 9, 16, 10.1186/s13072-016-0064-6 Pandya-Jones, 2020, A protein assembly mediates Xist localization and gene silencing, Nature, 587, 145, 10.1038/s41586-020-2703-0 Ridings-Figueroa, 2017, The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory, Genes Dev, 31, 876, 10.1101/gad.295907.117 Sunwoo, 2017, Repeat E anchors Xist RNA to the inactive X chromosomal compartment through CDKN1A-interacting protein (CIZ1), Proc Natl Acad Sci U S A, 114, 10654, 10.1073/pnas.1711206114 Yue, 2017, Xist RNA repeat E is essential for ASH2L recruitment to the inactive X and regulates histone modifications and escape gene expression, PLoS Genet, 13, 10.1371/journal.pgen.1006890 Monfort, 2015, Identification of spen as a crucial factor for xist function through forward genetic screening in haploid embryonic stem cells, Cell Rep, 12, 554, 10.1016/j.celrep.2015.06.067 Dossin, 2020, SPEN integrates transcriptional and epigenetic control of X-inactivation, Nature, 578, 455, 10.1038/s41586-020-1974-9 McHugh, 2015, The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3, Nature, 521, 232, 10.1038/nature14443 Schoeftner, 2006, Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing, EMBO J, 25, 3110, 10.1038/sj.emboj.7601187 Almeida, 2017, PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation, Science, 356, 1081, 10.1126/science.aal2512 Bousard, 2019, The role of Xist-mediated Polycomb recruitment in the initiation of X-chromosome inactivation, EMBO Rep, 20, 10.15252/embr.201948019 Pintacuda, 2017, hnRNPK recruits PCGF3/5-PRC1 to the Xist RNA B-repeat to establish polycomb-mediated chromosomal silencing, Mol Cell, 68, 955, 10.1016/j.molcel.2017.11.013 Lee, 2013, X-inactivation, imprinting, and long noncoding RNAs in health and disease, Cell, 152, 1308, 10.1016/j.cell.2013.02.016 Dixon-McDougall, 2021, Independent domains for recruitment of PRC1 and PRC2 by human XIST, PLoS Genet, 17, 10.1371/journal.pgen.1009123 Patil, 2016, m(6)A RNA methylation promotes XIST-mediated transcriptional repression, Nature, 537, 369, 10.1038/nature19342 Coker, 2020, The role of the Xist 5' m6A region and RBM15 in X chromosome inactivation, Wellcome Open Res, 5, 31, 10.12688/wellcomeopenres.15711.1 Engreitz, 2013, The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome, Science, 341, 1237973, 10.1126/science.1237973 Jeon, 2011, YY1 tethers Xist RNA to the inactive X nucleation center, Cell, 146, 119, 10.1016/j.cell.2011.06.026 Chen, 2016, Xist recruits the X chromosome to the nuclear Lamina to enable chromosome-wide silencing, Science, 354, 468, 10.1126/science.aae0047 Colognori, 2019, Xist deletional analysis reveals an interdependency between xist RNA and polycomb complexes for spreading along the inactive X, Mol Cell, 74, 101, 10.1016/j.molcel.2019.01.015 Wutz, 2000, A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation, Mol Cell, 5, 695, 10.1016/S1097-2765(00)80248-8 Chan, 2011, Diverse factors are involved in maintaining X chromosome inactivation, Proc Natl Acad Sci U S A, 108, 16699, 10.1073/pnas.1107616108 Schultz, 2002, SETDB1:a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins, Genes Dev, 16, 919, 10.1101/gad.973302 Lopes-Ramos, 2020, Genome-wide sex and gender differences in cancer, Front Oncol, 10, 597788, 10.3389/fonc.2020.597788 Siegel, 2021, Cancer statistics, 2021, CA Cancer J Clin, 71, 7, 10.3322/caac.21654 Libert, 2010, The X chromosome in immune functions: when a chromosome makes the difference, Nat Rev Immunol, 10, 594, 10.1038/nri2815 Park, 2020, Sex-bias in COVID-19-associated illness severity and mortality in cancer patients: a systematic review and meta-analysis, EClinicalMedicine, 26, 100519, 10.1016/j.eclinm.2020.100519 Brodin, 2021, Immune determinants of COVID-19 disease presentation and severity, Nat Med, 27, 28, 10.1038/s41591-020-01202-8 Wenham, 2020, Gender and COVID-19 Working Group. COVID-19:the gendered impacts of the outbreak, Lancet, 395, 846, 10.1016/S0140-6736(20)30526-2 Li, 2020, Sex differences in oncogenic mutational processes, Nat Commun, 11, 4330, 10.1038/s41467-020-17359-2 Zhu, 2019, Sex disparities in cancer, Cancer Lett, 466, 35, 10.1016/j.canlet.2019.08.017 Galasso, 2020, Gender differences in COVID-19 attitudes and behavior: panel evidence from eight countries, Proc Natl Acad Sci U S A, 117, 27285, 10.1073/pnas.2012520117 Vlassoff, 2007, Gender differences in determinants and consequences of health and illness, J Health Popul Nutr, 25, 47 Klein, 2016, Sex differences in immune responses, Nat Rev Immunol, 16, 626, 10.1038/nri.2016.90 Youness, 2021, Escape from X chromosome inactivation and the female predominance in autoimmune diseases, Int J Mol Sci, 22, 1114, 10.3390/ijms22031114 Fish, 2008, The X-files in immunity: sex-based differences predispose immune responses, Nat Rev Immunol, 8, 737, 10.1038/nri2394 Pinheiro, 2011, X-chromosome-located microRNAs in immunity: might they explain male/female differences? The X chromosome-genomic context may affect X-located miRNAs and downstream signaling, thereby contributing to the enhanced immune response of females, Bioessays, 33, 791, 10.1002/bies.201100047 Berletch, 2015, Escape from X inactivation varies in mouse tissues, PLoS Genet, 11, e1005079, 10.1371/journal.pgen.1005079 Carrel, 2005, X-inactivation profile reveals extensive variability in X-linked gene expression in females, Nature, 434, 400, 10.1038/nature03479 Tukiainen, 2017, Landscape of X chromosome inactivation across human tissues, Nature, 550, 244, 10.1038/nature24265 Balaton, 2015, Derivation of consensus inactivation status for X-linked genes from genome-wide studies, Biol Sex Differ, 6, 35, 10.1186/s13293-015-0053-7 Pyfrom, 2021, The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients, Proc Natl Acad Sci U S A, 118, 10.1073/pnas.2024624118 Syrett, 2019, Altered X-chromosome inactivation in T cells may promote sex-biased autoimmune diseases, JCI Insight, 4, 10.1172/jci.insight.126751 Syrett, 2018, Diversity of epigenetic features of the inactive X-chromosome in NK cells, dendritic cells, and macrophages, Front Immunol, 9, 3087, 10.3389/fimmu.2018.03087 Wang, 2016, Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X, Proc Natl Acad Sci U S A, 113, E2029, 10.1073/pnas.1520113113 Syrett, 2017, Loss of Xist RNA from the inactive X during B cell development is restored in a dynamic YY1-dependent two-step process in activated B cells, PLoS Genet, 13, 10.1371/journal.pgen.1007050 Cancro, 2020, Age-associated B cells, Annu Rev Immunol, 38, 315, 10.1146/annurev-immunol-092419-031130 Karnell, 2017, Role of CD11c + T-bet + B cells in human health and disease, Cell Immunol, 321, 40, 10.1016/j.cellimm.2017.05.008 Celhar, 2012, TLR7 and TLR9 in SLE: when sensing self Goes wrong, Immunol Res, 53, 58, 10.1007/s12026-012-8270-1 Woodruff, 2020, Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19, Nat Immunol, 21, 1506, 10.1038/s41590-020-00814-z Dunford, 2017, Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias, Nat Genet, 49, 10, 10.1038/ng.3726 Pinto, 2015, Genomic landscape of paediatric adrenocortical tumours, Nat Commun, 6, 6302, 10.1038/ncomms7302 Jiang, 2015, Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma, Nat Genet, 47, 1061, 10.1038/ng.3358 Dalgliesh, 2010, Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes, Nature, 463, 360, 10.1038/nature08672 Ntziachristos, 2014, Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia, Nature, 514, 513, 10.1038/nature13605 Shi, 2021, UTX condensation underlies its tumour-suppressive activity, Nature, 597, 726, 10.1038/s41586-021-03903-7 van Haaften, 2009, Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer, Nat Genet, 41, 521, 10.1038/ng.349 Van der Meulen, 2015, The H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia, Blood, 125, 13, 10.1182/blood-2014-05-577270 Kaneko, 2018, X chromosome protects against bladder cancer in females via a KDM6A-dependent epigenetic mechanism, Sci Adv, 4, eaar5598, 10.1126/sciadv.aar5598 Hu, 2017, Long non-coding RNA XIST promotes cell growth and metastasis through regulating miR-139-5p mediated Wnt/β-catenin signaling pathway in bladder cancer, Oncotarget, 8, 94554, 10.18632/oncotarget.21791 Fang, 2016, Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2 expression, Biochem Biophys Res Commun, 478, 811, 10.1016/j.bbrc.2016.08.030 Liu, 2019, Upregulation of long noncoding RNA XIST is associated with poor prognosis in human cancers, J Cell Physiol, 234, 6594, 10.1002/jcp.27400 Liu, 2019, LncRNA XIST facilitates proliferation and epithelial-mesenchymal transition of colorectal cancer cells through targeting miR-486-5p and promoting neuropilin-2, J Cell Physiol, 234, 13747, 10.1002/jcp.28054 Sun, 2018, Long non-coding RNA XIST sponges miR-34a to promotes colon cancer progression via Wnt/β-catenin signaling pathway, Gene, 665, 141, 10.1016/j.gene.2018.04.014 Song, 2017, Long non-coding RNA XIST functions as an oncogene in human colorectal cancer by targeting miR-132-3p, J BUON, 22, 696 Sun, 2017, Knockdown of lncRNA-XIST enhances the chemosensitivity of NSCLC cells via suppression of autophagy, Oncol Rep, 38, 3347 Wang, 2017, The long non-coding RNA XIST controls non-small cell lung cancer proliferation and invasion by modulating miR-186-5p, Cell Physiol Biochem, 41, 2221, 10.1159/000475637 Zhang, 2017, The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancer, Acta Pharmacol Sin, 38, 371, 10.1038/aps.2016.133 Zhou, 2019, XIST promote the proliferation and migration of non-small cell lung cancer cells via sponging miR-16 and regulating CDK8 expression, Am J Transl Res, 11, 6196 Zhang, 2019, Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) plays a critical role in predicting clinical prognosis and progression of colorectal cancer, Med Sci Monit, 25, 6429, 10.12659/MSM.915329 Hu, 2019, Long noncoding RNA XIST participates in bladder cancer by downregulating p53 via binding to TET1, J Cell Biochem, 120, 6330, 10.1002/jcb.27920 Liu, 2018, Long noncoding RNA XIST regulates miR-137-EZH2 axis to promote tumor metastasis in colorectal cancer, Oncol Res, 27, 99, 10.3727/096504018X15195193936573 Xu, 2018, LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells, Cancer Cell Int, 18, 41, 10.1186/s12935-018-0540-0 Zhou, 2019, Long non-coding RNA XIST promotes cell proliferation and migration through targeting miR-133a in bladder cancer, Exp Ther Med, 18, 3475 Li, 2018, Long non-coding RNA XIST promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer, Cancer Lett, 418, 185, 10.1016/j.canlet.2018.01.036 Qiu, 2019, Downregulation of long non-coding RNA XIST inhibits cell proliferation, migration, invasion and EMT by regulating miR-212-3p/CBLL1 axis in non-small cell lung cancer cells, Eur Rev Med Pharmacol Sci, 23, 8391 Jiang, 2020, Knockdown of lncRNA XIST suppresses cell tumorigenicity in human non-small cell lung cancer by regulating miR-142-5p/PAX6 axis, Onco Targets Ther, 13, 4919, 10.2147/OTT.S238808 Rong, 2020, Long non-coding RNA XIST expedites lung adenocarcinoma progression through upregulating MDM2 expression via binding to miR-363-3p, Thorac Cancer, 11, 659, 10.1111/1759-7714.13310 Wang, 2018, Knockdown of LncRNA-XIST suppresses proliferation and TGF-β1-induced EMT in NSCLC through the Notch-1 pathway by regulation of miR-137, Genet Test Mol Biomarkers, 22, 333, 10.1089/gtmb.2018.0026 Xiong, 2017, The long non-coding RNA XIST interacted with miR-124 to modulate bladder cancer growth, invasion and migration by targeting androgen receptor (AR), Cell Physiol Biochem, 43, 405, 10.1159/000480419 Lombard, 2015, The emerging role of the androgen receptor in bladder cancer, Endocr Relat Cancer, 22, 10.1530/ERC-15-0209 Laor, 1985, Androgen receptors in bladder tumors, Urology, 25, 161, 10.1016/0090-4295(85)90534-5 Miyamoto, 2007, Promotion of bladder cancer development and progression by androgen receptor signals, J Natl Cancer Inst, 99, 558, 10.1093/jnci/djk113 Garg, 2019, WNT/β-catenin signaling in urothelial carcinoma of bladder, World J Nephrol, 8, 83, 10.5527/wjn.v8.i5.83 Overdevest, 2012, CD24 expression is important in male urothelial tumorigenesis and metastasis in mice and is androgen regulated, Proc Natl Acad Sci U S A, 109, 10.1073/pnas.1113960109 Groenendijk, 2016, ERBB2 mutations characterize a subgroup of muscle-invasive bladder cancers with excellent response to neoadjuvant chemotherapy, Eur Urol, 69, 384, 10.1016/j.eururo.2015.01.014 Inoue, 2018, ELK1 promotes urothelial tumorigenesis in the presence of an activated androgen receptor, Am J Cancer Res, 8, 2325 Zhao, 2014, Androgen receptor expression in male breast cancer predicts inferior outcome and poor response to tamoxifen treatment, Eur J Endocrinol, 171, 527, 10.1530/EJE-14-0278 Chen, 2017, Long noncoding RNA XIST expedites metastasis and modulates epithelial-mesenchymal transition in colorectal cancer, Cell Death Dis, 8, 10.1038/cddis.2017.421 Zhang, 2019, Atractylenolide II reverses the influence of lncRNA XIST/miR-30a-5p/ROR1 axis on chemo-resistance of colorectal cancer cells, J Cell Mol Med, 23, 3151, 10.1111/jcmm.14148 Yang, 2020, LncRNA XIST modulates HIF-1A/AXL signaling pathway by inhibiting miR-93-5p in colorectal cancer, Mol Genet Genomic Med, 8, e1112, 10.1002/mgg3.1112 Li, 2021, Long noncoding RNA XIST knockdown suppresses the growth of colorectal cancer cells via regulating microRNA-338-3p/PAX5 axis, Eur J Cancer Prev, 30, 132, 10.1097/CEJ.0000000000000596 Zeng, 2021, The lncRNA XIST/miR-125b-2-3p axis modulates cell proliferation and chemotherapeutic sensitivity via targeting Wee1 in colorectal cancer, Cancer Med, 10, 2423, 10.1002/cam4.3777 Yip, 2008, Bcl-2 family proteins and cancer, Oncogene, 27, 6398, 10.1038/onc.2008.307 Firestein, 2008, CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity, Nature, 455, 547, 10.1038/nature07179 Marei, 2021, p53 signaling in cancer progression and therapy, Cancer Cell Int, 21, 703, 10.1186/s12935-021-02396-8 Yang, 2020, METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST, Mol Cancer, 19, 46, 10.1186/s12943-020-1146-4 Sung, 2021, Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J Clin, 71, 209, 10.3322/caac.21660 Zheng, 2018, Long non-coding RNA XIST inhibited breast cancer cell growth, migration, and invasion via miR-155/CDX1 axis, Biochem Biophys Res Commun, 498, 1002, 10.1016/j.bbrc.2018.03.104 Huang, 2016, Xist reduction in breast cancer upregulates AKT phosphorylation via HDAC3-mediated repression of PHLPP1 expression, Oncotarget, 7, 43256, 10.18632/oncotarget.9673 Liu, 2021, Long noncoding RNA XIST acts as a ceRNA of miR-362-5p to suppress breast cancer progression, Cancer Biother Radiopharm, 36, 456 Xing, 2018, Loss of XIST in breast cancer activates MSN-c-Met and reprograms microglia via exosomal miRNA to promote brain metastasis, Cancer Res, 78, 4316, 10.1158/0008-5472.CAN-18-1102 Kim, 2014, UTX and MLL4 coordinately regulate transcriptional programs for cell proliferation and invasiveness in breast cancer cells, Cancer Res, 74, 1705, 10.1158/0008-5472.CAN-13-1896 Xu, 2018, Long noncoding RNA XIST promotes proliferation and invasion by targeting miR-141 in papillary thyroid carcinoma, Onco Targets Ther, 11, 5035, 10.2147/OTT.S170439 Liu, 2018, LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling, J Exp Clin Cancer Res, 37, 279, 10.1186/s13046-018-0950-9 Du, 2021, LncRNA XIST promotes migration and invasion of papillary thyroid cancer cell by modulating miR-101-3p/CLDN1 axis, Biochem Genet, 59, 437, 10.1007/s10528-020-09985-8 Hu, 2020, Long non-coding RNA XIST is down-regulated and correlated to better prognosis in ovarian cancer, Math Biosci Eng, 17, 2070, 10.3934/mbe.2020110 Huang, 2020, XIST lost induces ovarian cancer stem cells to acquire taxol resistance via a KMT2C-dependent way, Cancer Cell Int, 20, 436, 10.1186/s12935-020-01500-8 Wang, 2018, Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p, J Gynecol Oncol, 29, e99, 10.3802/jgo.2018.29.e99 Guo, 2021, Upregulation of long noncoding RNA XIST has anticancer effects on ovarian cancer through sponging miR-106a, Hum Cell, 34, 579, 10.1007/s13577-020-00469-w Huang, 2002, Relationship of XIST expression and responses of ovarian cancer to chemotherapy, Mol Cancer Ther, 1, 769 Meng, 2021, Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis, World J Surg Oncol, 19, 165, 10.1186/s12957-021-02274-7 Jiang, 2021, Inhibition of long non-coding RNA XIST upregulates microRNA-149-3p to repress ovarian cancer cell progression, Cell Death Dis, 12, 145, 10.1038/s41419-020-03358-0 Zhu, 2018, LncRNA XIST accelerates cervical cancer progression via upregulating Fus through competitively binding with miR-200a, Biomed Pharmacother, 105, 789, 10.1016/j.biopha.2018.05.053 Chen, 2019, Up-regulated lncRNA XIST contributes to progression of cervical cancer via regulating miR-140-5p and ORC1, Cancer Cell Int, 19, 45, 10.1186/s12935-019-0744-y Liu, 2020, Long noncoding RNA XIST contributes to cervical cancer development through targeting miR-889-3p/SIX1 axis, Cancer Biother Radiopharm, 35, 640 Gong, 2008, Analysis of X chromosome inactivation in autism spectrum disorders, Am J Med Genet B Neuropsychiatr Genet, 147B, 830, 10.1002/ajmg.b.30688 Guo, 2022, Sex differences in Alzheimer's disease: insights from the multiomics landscape, Biol Psychiatr, 91, 61, 10.1016/j.biopsych.2021.02.968 Brand, 2021, The impact of X-chromosome inactivation on phenotypic expression of X-linked neurodevelopmental disorders, Brain Sci, 11, 904, 10.3390/brainsci11070904 Plenge, 1997, A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation, Nat Genet, 17, 353, 10.1038/ng1197-353 Talebizadeh, 2005, Brief report: non-random X chromosome inactivation in females with autism, J Autism Dev Disord, 35, 675, 10.1007/s10803-005-0011-z Sripathy, 2017, Screen for reactivation of MeCP2 on the inactive X chromosome identifies the BMP/TGF-β superfamily as a regulator of XIST expression, Proc Natl Acad Sci U S A, 114, 1619, 10.1073/pnas.1621356114 Good, 2021, MeCP2:the genetic driver of rett syndrome epigenetics, Front Genet, 12, 620859, 10.3389/fgene.2021.620859 Amir, 1999, Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2, Nat Genet, 23, 185, 10.1038/13810 Xiol, 2019, X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients, Sci Rep, 9, 11983, 10.1038/s41598-019-48385-w Wang, 2016, Regulation of LRRK2 promoter activity and gene expression by Sp1, Mol Brain, 9, 33, 10.1186/s13041-016-0215-5 Lee, 2012, Leucine-rich repeat kinase 2 (LRRK2) as a potential therapeutic target in Parkinson's disease, Trends Pharmacol Sci, 33, 365, 10.1016/j.tips.2012.04.001 Cao, 2018, Leucine-rich repeat kinase 2 aggravates secondary brain injury induced by intracerebral hemorrhage in rats by regulating the P38 MAPK/Drosha pathway, Neurobiol Dis, 119, 53, 10.1016/j.nbd.2018.07.024 Di Maio, 2018, LRRK2 activation in idiopathic Parkinson's disease, Sci Transl Med, 10, eaar5429, 10.1126/scitranslmed.aar5429 Zhou, 2021, LncRNA XIST sponges miR-199a-3p to modulate the Sp1/LRRK2 signal pathway to accelerate Parkinson's disease progression, Aging (Albany NY), 13, 4115, 10.18632/aging.202378 Du, 2020, Silencing of long noncoding RNA XIST attenuated Alzheimer's disease-related BACE1 alteration through miR-124, Cell Biol Int, 44, 630, 10.1002/cbin.11263 Yan, 2022, lncRNA XIST induces Aβ accumulation and neuroinflammation by the epigenetic repression of NEP in Alzheimer's disease, J Neurogenet, 36, 11, 10.1080/01677063.2022.2028784 Qin, 2020, Sex differences in the proliferation of pulmonary artery endothelial cells: implications for plexiform arteriopathy, J Cell Sci, 133, jcs237776, 10.1242/jcs.237776 Batton, 2018, Sex differences in pulmonary arterial hypertension: role of infection and autoimmunity in the pathogenesis of disease, Biol Sex Differ, 9, 15, 10.1186/s13293-018-0176-8 Qin, 2021, Up-regulation of the long noncoding RNA X-inactive-specific transcript and the sex bias in pulmonary arterial hypertension, Am J Pathol, 191, 1135, 10.1016/j.ajpath.2021.03.009 Patel, 2013, A novel p38 mitogen-activated protein kinase/Elk-1 transcription factor-dependent molecular mechanism underlying abnormal endothelial cell proliferation in plexogenic pulmonary arterial hypertension, J Biol Chem, 288, 25701, 10.1074/jbc.M113.502674 Atkins, 2007, Role of Krüppel-like transcription factors in endothelial biology, Circ Res, 100, 1686, 10.1161/01.RES.0000267856.00713.0a Shapiro, 2012, Sex differences in the diagnosis, treatment, and outcome of patients with pulmonary arterial hypertension enrolled in the registry to evaluate early and long-term pulmonary arterial hypertension disease management, Chest, 141, 363, 10.1378/chest.10-3114 Mair, 2014, Pulmonary arterial hypertension: basis of sex differences in incidence and treatment response, Br J Pharmacol, 171, 567, 10.1111/bph.12281 Xu, 2010, Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the expression of p27kip1 in rats, Respir Res, 11, 182, 10.1186/1465-9921-11-182 Yuan, 2013, Oestradiol ameliorates monocrotaline pulmonary hypertension via NO, prostacyclin and endothelin-1 pathways, Eur Respir J, 41, 1116, 10.1183/09031936.00044112 Ye, 2011, Atractylenolide II induces G1 cell-cycle arrest and apoptosis in B16 melanoma cells, J Ethnopharmacol, 136, 279, 10.1016/j.jep.2011.04.020 Huang, 2019, Platycodin D triggers the extracellular release of programed death Ligand-1 in lung cancer cells, Food Chem Toxicol, 131, 110537, 10.1016/j.fct.2019.05.045 Peng, 2019, miR-34a enhances the susceptibility of gastric cancer to platycodin D by targeting survivin, Pathobiology, 86, 296, 10.1159/000502913 Lu, 2015, Proteomic analysis of hepatocellular carcinoma HepG2 cells treated with platycodin D, Chin J Nat Med, 13, 673 Chen, 2020, Platycodin D (PD) regulates LncRNA-XIST/miR-335 axis to slow down bladder cancer progression in vitro and in vivo, Exp Cell Res, 396, 112281, 10.1016/j.yexcr.2020.112281 Chen, 2021, Long non-coding RNAs: from disease code to drug role, Acta Pharm Sin B, 11, 340, 10.1016/j.apsb.2020.10.001 Setten, 2019, The Current state and future directions of RNAi-based therapeutics, Nat Rev Drug Discov, 18, 421, 10.1038/s41573-019-0017-4 Rinaldi, 2018, Antisense oligonucleotides: the next frontier for treatment of neurological disorders, Nat Rev Neurol, 14, 9, 10.1038/nrneurol.2017.148 Gardiner, 2010, Molecular basis of pharmacotherapies for cognition in Down syndrome, Trends Pharmacol Sci, 31, 66, 10.1016/j.tips.2009.10.010 Jiang, 2013, Translating dosage compensation to trisomy 21, Nature, 500, 296, 10.1038/nature12394 Chiang, 2018, Trisomy silencing by XIST normalizes Down syndrome cell pathogenesis demonstrated for hematopoietic defects in vitro, Nat Commun, 9, 5180, 10.1038/s41467-018-07630-y Spiering, 2021, Why females do better: the X chromosomal TLR7 gene-dose effect in COVID-19, Front Immunol, 12, 756262, 10.3389/fimmu.2021.756262 Kopp, 2018, Functional classification and experimental dissection of long noncoding RNAs, Cell, 172, 393, 10.1016/j.cell.2018.01.011