{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LINC00961 is a multifunctional long non‐coding RNA that plays context‐dependent roles in tissue homeostasis, regeneration, angiogenesis, and tumorigenesis. In skeletal muscle, for example, LINC00961 encodes a small regulatory polypeptide (SPAAR) that localizes to late endosomes/lysosomes and interacts with the lysosomal v‐ATPase to negatively regulate amino acid–induced mTORC1 activation, a mechanism that modulates muscle regeneration after injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In vascular endothelial cells, LINC00961 expression is upregulated during differentiation and the locus produces both the transcript and SPAAR, which exert opposing effects on processes such as adhesion, tube formation, migration, and barrier integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In several cancers—including non‐small cell lung cancer, skin melanoma, glioma, colon cancer, renal cell carcinoma, hepatocellular carcinoma, oral squamous cell carcinoma, and luminal breast cancer—LINC00961 is frequently downregulated. Its tumor‐suppressive functions involve inhibition of cell proliferation, migration, invasion, and epithelial–mesenchymal transition via modulation of signaling pathways (such as Wnt/β‐catenin, PI3K/AKT) and by acting as a competing endogenous RNA that sponges oncogenic microRNAs to upregulate tumor‐suppressor genes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "13"}]}, {"type": "t", "text": " In contrast, in certain contexts such as cisplatin‐resistant ovarian cancer and hypoxic cardiomyocytes, elevated LINC00961 expression has been observed; in the former case, it is one of several transcripts upregulated in resistant cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", while in cardiomyocytes, STAT1‐mediated transcriptional activation of LINC00961 aggravates hypoxia‐induced injury via modulation of PI3K/AKT/GSK3β signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Moreover, studies in vascular smooth muscle cells indicate that reduced LINC00961 levels promote proliferation and inhibit apoptosis through interactions with miR‑367."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Collectively, these findings underscore the tissue‐ and context‐specific roles of LINC00961, highlighting its dual capacity as a non‐coding transcript and as an mRNA for a functional micropeptide. Its involvement in multiple signaling pathways and biological processes positions LINC00961 as a promising diagnostic biomarker and therapeutic target in diseases ranging from muscle injury and cardiovascular disorders to a variety of cancers"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "–."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Akinobu Matsumoto, Alessandra Pasut, Masaki Matsumoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature21034"}], "href": "https://doi.org/10.1038/nature21034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28024296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28024296"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shahragim Tajbakhsh "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA-Encoded Polypeptide SPAR(s) with mTORC1 to Regulate Skeletal Muscle Regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2017.03.016"}], "href": "https://doi.org/10.1016/j.stem.2017.03.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28388426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28388426"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nathalie Rion, Markus A Rüegg "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA-encoded peptides: More than translational noise?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2017.35"}], "href": "https://doi.org/10.1038/cr.2017.35"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28290465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28290465"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Helen L Spencer, Rachel Sanders, Mounia Boulberdaa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The LINC00961 transcript and its encoded micropeptide, small regulatory polypeptide of amino acid response, regulate endothelial cell function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvaa008"}], "href": "https://doi.org/10.1093/cvr/cvaa008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31990292"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31990292"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ana-Mishel Spiroski, Rachel Sanders, Marco Meloni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22020969"}], "href": "https://doi.org/10.3390/ijms22020969"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33478078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33478078"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Bin Jiang, Jing Liu, Yu-Hong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA LINC00961 inhibits cell invasion and metastasis in human non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2017.11.062"}], "href": "https://doi.org/10.1016/j.biopha.2017.11.062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29156520"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29156520"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xin Mu, Kuan-Hou Mou, Rui Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Linc00961 inhibits the proliferation and invasion of skin melanoma by targeting the miR‑367/PTEN axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2019.4848"}], "href": "https://doi.org/10.3892/ijo.2019.4848"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31364744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31364744"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dongming Chen, Meng Zhu, Huang Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC00961 restrains cancer progression via modulating epithelial-mesenchymal transition in renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.27483"}], "href": "https://doi.org/10.1002/jcp.27483"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30367453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30367453"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "X-W Lu, N Xu, Y-G Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of long noncoding RNA LINC00961 suppresses glioma metastasis and correlates with favorable prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_201808_15630"}], "href": "https://doi.org/10.26355/eurrev_201808_15630"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30070327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30070327"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Haixia Wu, Yuedi Dai, Dexiang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC00961 inhibits the migration and invasion of colon cancer cells by sponging miR-223-3p and targeting SOX11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.2850"}], "href": "https://doi.org/10.1002/cam4.2850"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32045135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32045135"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Lixia Zhang, Linqin Shao, Ying Hu "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA LINC00961 inhibited cell proliferation and invasion through regulating the Wnt/β-catenin signaling pathway in tongue squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.28509"}], "href": "https://doi.org/10.1002/jcb.28509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30854692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30854692"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "L-N Pan, Y-R Sun "}, {"type": "b", "children": [{"type": "t", "text": "LINC00961 suppresses cell proliferation and induces cell apoptosis in oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_201904_17699"}], "href": "https://doi.org/10.26355/eurrev_201904_17699"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31081090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31081090"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Zhiwen Huang, Wei Lei, Jin Tan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA LINC00961 inhibits cell proliferation and induces cell apoptosis in human non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.27166"}], "href": "https://doi.org/10.1002/jcb.27166"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30010215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30010215"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Zhi-Guo Zheng, Hong Xu, Sha-Sha Suo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep26093"}], "href": "https://doi.org/10.1038/srep26093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27193186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27193186"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Shengzhong Liu, Ying He, Jun Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STAT1-avtiviated LINC00961 regulates myocardial infarction by the PI3K/AKT/GSK3β signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.28596"}], "href": "https://doi.org/10.1002/jcb.28596"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30887575"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30887575"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "C-T Wu, S Liu, M Tang "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of linc00961 contributes to promote proliferation and inhibit apoptosis of vascular smooth muscle cell by sponging miR-367 in patients with coronary heart disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_201910_19168"}], "href": "https://doi.org/10.26355/eurrev_201910_19168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31646586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31646586"}]}]}]}