{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nExtensive research on SIX family transcription factors in muscle physiology and development has revealed that these proteins play crucial yet divergent roles in the regulation of satellite cell proliferation, differentiation, and overall muscle homeostasis. For example, studies have shown that SIX1 activates myogenin expression and promotes differentiation of satellite cells, whereas SIX4 and SIX5 can inhibit proliferation and differentiation, respectively, thereby influencing muscle regeneration and the progression of disorders such as myotonic dystrophy and cardiac conduction abnormalities."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to governing muscle cell behavior, reduced gene dosage of SIX4 and SIX5 has been associated with congenital malformations such as omphalocele and has been shown to improve muscle pathology in dystrophic mouse models, highlighting their broader impact on tissue development and repair. These studies underscore the importance of SIX gene dosage in ensuring proper growth, cell survival, and morphological transformations in both muscle and non‐muscle tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA distinct regulatory network operating in breast cancer further illustrates the interplay between non‐coding RNAs and cellular apoptotic pathways. Here, the long non‐coding RNA TPT1‑AS1 acts as a competing endogenous RNA by sponging miR‑3156‑5p—which is functionally related to the MIR3156‑2 microRNA—and thereby relieves the repression on caspase‑2 (CASP2), a proapoptotic factor. This mechanism culminates in diminished cellular proliferation and enhanced sensitivity to chemotherapy, underscoring a tumor‑suppressive role for the miR‑3156‑5p/MIR3156‑2 axis in breast cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hiroko Wakimoto, Colin T Maguire, Megan C Sherwood, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of cardiac conduction system abnormalities in mice with targeted disruption of Six5 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Interv Card Electrophysiol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/a:1020881520353"}], "href": "https://doi.org/10.1023/a:1020881520353"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12397222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12397222"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Partha S Sarkar, Sharan Paul, Jennifer Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Six5 is required for spermatogenic cell survival and spermiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddh161"}], "href": "https://doi.org/10.1093/hmg/ddh161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15163633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15163633"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kirkwood E Personius, Joyti Nautiyal, Sita Reddy "}, {"type": "b", "children": [{"type": "t", "text": "Myotonia and muscle contractile properties in mice with SIX5 deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Muscle Nerve (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mus.20239"}], "href": "https://doi.org/10.1002/mus.20239"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15536612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15536612"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anna Matynia, Carina Hoi Ng, Warunee Dansithong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muscleblind1, but not Dmpk or Six5, contributes to a complex phenotype of muscular and motivational deficits in mouse models of myotonic dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0009857"}], "href": "https://doi.org/10.1371/journal.pone.0009857"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20360842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20360842"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hiroshi Yajima, Norio Motohashi, Yusuke Ono, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Six family genes control the proliferation and differentiation of muscle satellite cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2010.08.001"}], "href": "https://doi.org/10.1016/j.yexcr.2010.08.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20696153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20696153"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hiroshi Yajima, Kiyoshi Kawakami "}, {"type": "b", "children": [{"type": "t", "text": "Low Six4 and Six5 gene dosage improves dystrophic phenotype and prolongs life span of mdx mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Growth Differ (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/dgd.12290"}], "href": "https://doi.org/10.1111/dgd.12290"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27224259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27224259"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Masanori Takahashi, Masaru Tamura, Shigeru Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mice doubly deficient in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Six4"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Six5"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " show ventral body wall defects reproducing human omphalocele."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Model Mech (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dmm.034611"}], "href": "https://doi.org/10.1242/dmm.034611"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30237319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30237319"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yuan Huang, Yabing Zheng, Xiying Shao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA TPT1-AS1 sensitizes breast cancer cell to paclitaxel and inhibits cell proliferation by miR-3156-5p/caspase 2 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-021-00541-z"}], "href": "https://doi.org/10.1007/s13577-021-00541-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33999360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33999360"}]}]}]}