{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LINC00998 has been implicated in cancer through distinct, context‐dependent mechanisms. In hepatocellular carcinoma, LINC00998 encodes a small endogenous peptide named SMIM30. Rather than acting as a non‐coding RNA per se, SMIM30 promotes tumorigenesis by enhancing cell proliferation and migration. Mechanistically, SMIM30 is transcriptionally activated by c‐Myc and facilitates the membrane anchoring and phosphorylation of the non‐receptor tyrosine kinases SRC/YES1, which in turn activate the downstream MAPK signaling cascade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, studies in glioma and acute myeloid leukemia reveal a tumor‐suppressive role for LINC00998. In glioma, LINC00998 is downregulated, and its overexpression impairs cell proliferation and arrests the cell cycle at the G1/S transition. It exerts these effects through binding to CBX3, thereby stabilizing this protein against ubiquitination and regulating the c‐Met/Akt/mTOR pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, in acute myeloid leukemia, reduced levels of LINC00998 are associated with relapse and poor prognosis. Overexpression of LINC00998 in AML cells diminishes viability and colony formation while promoting apoptosis; these effects are mediated via its interaction with ZFP36, which enhances the decay of mTORC2, a proto‐oncogene in this setting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yanan Pang, Zhiyong Liu, Huan Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Peptide SMIM30 promotes HCC development by inducing SRC/YES1 membrane anchoring and MAPK pathway activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hepatol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jhep.2020.05.028"}], "href": "https://doi.org/10.1016/j.jhep.2020.05.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32461121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32461121"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Haiping Cai, Yanjiao Yu, Xiangrong Ni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-03247-6"}], "href": "https://doi.org/10.1038/s41419-020-03247-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33268783"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33268783"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ximin Fang, Xiazhen Pan, Huirong Mai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC00998 functions as a novel tumor suppressor in acute myeloid leukemia via regulating the ZFP36 ring finger protein/mammalian target of rapamycin complex 2 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1996506"}], "href": "https://doi.org/10.1080/21655979.2021.1996506"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34699314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34699314"}]}]}]}