{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‑1299 has emerged as a pivotal regulatory microRNA in a spectrum of malignancies. In several studies, reduced miR‑1299 levels correlate with enhanced tumor cell proliferation, migration, invasion, and metastasis. For example, in hepatocellular carcinoma, downregulation of miR‑1299 leads to overexpression of cyclin‑dependent kinase 6 (CDK6) and accelerated cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, in triple‑negative breast cancer, high levels of circular RNA ciRS‑7, which harbors multiple binding sites for miR‑1299, serve as a competing endogenous RNA to sequester miR‑1299; this sponging effect subsequently elevates matrix metalloproteinases and promotes invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Further investigations in prostate cancer, cholangiocarcinoma, breast cancer, osteosarcoma, ovarian cancer, gastric cancer, and cervical cancer have demonstrated that miR‑1299 exerts tumor‑suppressive functions by directly targeting key oncogenes such as CDK6, STAT3, NOTCH3, PDPK1, and GBX2—underscoring its broad impact on malignancy progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have revealed that miR‑1299’s tumor‑suppressive capacity is frequently impaired by its sequestration within intricate competing endogenous RNA (ceRNA) networks. Multiple circular RNAs—such as ciRS‑7 in triple‑negative breast cancer, circ_0005230 in cholangiocarcinoma, hsa_circ_0136666 in breast cancer, and circ_ARF3 in osteosarcoma—as well as long non‑coding RNAs like KCNQ1OT1 in cervical cancer, have been shown to “sponge” miR‑1299. By binding to miR‑1299, these non‑coding RNAs limit its ability to repress oncogenic targets (e.g., CDK6, NOTCH3, PDPK1), thus indirectly promoting cell cycle progression and tumor aggressiveness.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond malignant contexts, miR‑1299 is implicated in several non‑cancerous conditions. In rheumatic heart disease, miR‑1299 is notably upregulated compared with healthy controls, suggesting a role in disease regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In melasma, miR‑1299 expression is inversely correlated with arginase‑2 levels, implicating it in the modulation of pigmentation through effects on autophagy and cellular senescence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Additionally, in drug‑resistant prolactinoma, elevated miR‑1299 targets and inhibits FOXO1, leading to enhanced prolactin secretion and contributing to therapeutic resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Preliminary findings in other pathologies—notably intracranial aneurysm and schizophrenia—further suggest that miR‑1299 may serve as a versatile modulator of cellular homeostasis in both oncologic and non‑oncologic settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Huaqiang Zhu, Guangchuan Wang, Xu Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-1299 suppresses cell proliferation of hepatocellular carcinoma (HCC) by targeting CDK6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2016.07.037"}], "href": "https://doi.org/10.1016/j.biopha.2016.07.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27490780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27490780"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yong Wang, Zhi Lu, Ningning Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-1299 is a negative regulator of STAT3 in colon cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2017.5605"}], "href": "https://doi.org/10.3892/or.2017.5605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28498395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28498395"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Meixiang Sang, Lingjiao Meng, Sihua Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA ciRS-7 Maintains Metastatic Phenotypes as a ceRNA of miR-1299 to Target MMPs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-18-0284"}], "href": "https://doi.org/10.1158/1541-7786.MCR-18-0284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30072582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30072582"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "F-B Zhang, Y Du, Y Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-1299 functions as a tumor suppressor to inhibit the proliferation and metastasis of prostate cancer by targeting NEK2."}]}, {"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_201901_16865"}], "href": "https://doi.org/10.26355/eurrev_201901_16865"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30720160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30720160"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yi Xu, Yue Yao, Yueping Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevation of circular RNA circ_0005230 facilitates cell growth and metastasis via sponging miR-1238 and miR-1299 in cholangiocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.101872"}], "href": "https://doi.org/10.18632/aging.101872"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30946694"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30946694"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Li-Hong Liu, Qing-Qing Tian, Juan Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of hsa_circ_0136666 contributes to breast cancer progression by sponging miR-1299 and targeting CDK6."}]}, {"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.28536"}], "href": "https://doi.org/10.1002/jcb.28536"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30993801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30993801"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ai-Mei Gao, Chunyan Yuan, Ai-Xin Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "circ_ARF3 regulates the pathogenesis of osteosarcoma by sponging miR-1299 to maintain CDK6 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2020.109622"}], "href": "https://doi.org/10.1016/j.cellsig.2020.109622"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32240746"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32240746"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xiufeng Yu, Ping Sheng, Jing Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The circular RNA circMAST1 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-1299 and regulating CTNND1 expression."}]}, {"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/s41419-020-2532-y"}], "href": "https://doi.org/10.1038/s41419-020-2532-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32393764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32393764"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yuqing Pei, Kexin Li, Xiaoying Lou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR‑1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2020.7623"}], "href": "https://doi.org/10.3892/or.2020.7623"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32468036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32468036"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yan-Yu Peng, Dan Sun, Yan Xin "}, {"type": "b", "children": [{"type": "t", "text": "Hsa_circ_0005230 is up-regulated and promotes gastric cancer cell invasion and migration via regulating the miR-1299/RHOT1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2022.2036514"}], "href": "https://doi.org/10.1080/21655979.2022.2036514"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35170374"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35170374"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yong-Hua Lin, Bao-Yan Zhang, Zhi-Chao Singh Chen "}, {"type": "b", "children": [{"type": "t", "text": "circRERE regulates the expression of GBX2 through miR-1299 and ZC3H13/N"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "6"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-methyladenosine (m"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "6"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "A) to promote growth and invasion of hepatocellular carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biosci (2022)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36222159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36222159"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Qian Yang, Jing Fu, Min Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-1299 is regulated by KCNQ1OT1 and inhibits cervical cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol (Noisy-le-grand) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14715/cmb/2023.69.10.24"}], "href": "https://doi.org/10.14715/cmb/2023.69.10.24"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37953567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37953567"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Ni Li, Jiangfang Lian, Sheng Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Detection of Differentially Expressed MicroRNAs in Rheumatic Heart Disease: miR-1183 and miR-1299 as Potential Diagnostic Biomarkers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2015/524519"}], "href": "https://doi.org/10.1155/2015/524519"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26539505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26539505"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Nan-Hyung Kim, Soo-Hyun Choi, Nayoung Yi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Arginase-2, a miR-1299 target, enhances pigmentation in melasma by reducing melanosome degradation via senescence-induced autophagy inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pigment Cell Melanoma Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/pcmr.12605"}], "href": "https://doi.org/10.1111/pcmr.12605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28627081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28627081"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Zheng Xiao, Zongming Wang, Bin Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-1299 promotes the synthesis and secretion of prolactin by inhibiting FOXO1 expression in drug-resistant prolactinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.09.070"}], "href": "https://doi.org/10.1016/j.bbrc.2019.09.070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31582213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31582213"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Hui Zhang, Bin Zhang, Chen Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA circLIFR regulates the proliferation, migration, invasion and apoptosis of human vascular smooth muscle cells via the miR-1299/KDR axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metab Brain Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11011-021-00853-x"}], "href": "https://doi.org/10.1007/s11011-021-00853-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34705228"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34705228"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Fangping Liao, Qingqing Zhong, Xueying Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Potential Immune-Related miRNAs Regulatory Network and Corresponding Diagnostic Efficacy in Schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11064-023-03940-w"}], "href": "https://doi.org/10.1007/s11064-023-03940-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37100927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37100927"}]}]}]}