{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTSIX is a long noncoding RNA that plays a pivotal role in mammalian X-chromosome inactivation by acting in antisense to XIST. In mice, TSIX is expressed early in development and helps orchestrate which X-chromosome is chosen to remain active by preventing the ectopic upregulation of Xist during differentiation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In this regulatory process, TSIX not only blocks Xist expression on the active X‐chromosome but also appears to work in conjunction with transcription factors, such as CTCF, to contribute to a dynamic epigenetic switch that controls X inactivation. Notably, while murine TSIX is essential for maintaining the active state once differentiation begins, its human counterpart, although evolutionarily truncated, is expressed during fetal stages, which may partly explain why X inactivation is not imprinted in the human placenta.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its critical function in X-chromosome regulation, TSIX has emerged as a broader regulatory molecule with implications in pathological processes. In systemic sclerosis, increased TSIX expression in dermal fibroblasts enhances the stability of type I collagen mRNA, suggesting TSIX contributes to the aberrant deposition of collagen observed in the disease; its upregulation appears to be mediated by TGF‑β signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, alterations in circulating TSIX levels have been incorporated into a novel RNA biomarker panel that, along with other epigenetic regulators, shows promise for the diagnosis and prognostic stratification of hepatocellular carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, studies examining serum TSIX levels in patients with spinal cord injury further indicate a potential role for TSIX as a noninvasive biomarker in diverse clinical settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "B R Migeon, A K Chowdhury, J A Dunston, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of TSIX, encoding an RNA antisense to human XIST, reveals differences from its murine counterpart: implications for X inactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/324022"}], "href": "https://doi.org/10.1086/324022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11555794"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11555794"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wendy Chao, Khanh D Huynh, Rebecca J Spencer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CTCF, a candidate trans-acting factor for X-inactivation choice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1065982"}], "href": "https://doi.org/10.1126/science.1065982"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11743158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11743158"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Srimonta Gayen, Emily Maclary, Emily Buttigieg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Primary Role for the Tsix lncRNA in Maintaining Random X-Chromosome Inactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2015.04.039"}], "href": "https://doi.org/10.1016/j.celrep.2015.04.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25981039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25981039"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhongzhi Wang, Masatoshi Jinnin, Kayo Nakamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA TSIX is upregulated in scleroderma dermal fibroblasts and controls collagen mRNA stabilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/exd.12900"}], "href": "https://doi.org/10.1111/exd.12900"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26566700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26566700"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alaa Habieb, Marwa Matboli, Hanaa El-Tayeb, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Potential role of lncRNA-TSIX, miR-548-a-3p, and SOGA1 mRNA in the diagnosis of hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-019-04810-x"}], "href": "https://doi.org/10.1007/s11033-019-04810-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31004302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31004302"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sara Mohammed Mohammed Salah, Marwa Matboli, Hanaa El-Tayeb Nasser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulation in the expression of (lncRNA-TSIX, TP53INP2 mRNA, miRNA-1283) in spinal cord injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygeno.2020.06.018"}], "href": "https://doi.org/10.1016/j.ygeno.2020.06.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32535070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32535070"}]}]}]}