{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐1228 is emerging as a multifunctional regulator with diverse roles in both neoplastic and non‐neoplastic contexts. In lung cancer, for example, decreased levels of circRNA hsa_circ_100395 lead to less sequestration of miR‐1228, thereby modulating TCF21 expression and impacting tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, systematic profiling of circulating microRNAs has identified miR‐1228 as one of the most stable endogenous controls across several cancer types, suggesting it functions as a housekeeping gene in the circulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the tumor microenvironment, miR‐1228 has been implicated in promoting oncogenic properties in multiple malignancies. In osteosarcoma, cancer‐associated fibroblasts (CAFs) package miR‐1228 into exosomes that, when transferred to tumor cells, downregulate the tumor suppressor SCAI and thereby enhance cell migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in breast cancer, up‐regulation of miR‐1228 has been reported to promote cell growth, invasion, and migration by targeting genes such as SCAI and MOAP1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while in HER‐2–positive breast cancer, a competing endogenous RNA (ceRNA) network involving circGFRA1 modulates the miR‐1228–AIFM2 axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In cervical cancer, functional knockdown studies employing ultrasound‐targeted microbubble destruction have further supported an oncogenic role for miR‐1228."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In hepatocellular carcinoma, beyond a separate line of investigation that characterizes miR‐1228’s function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", CAF‐derived extracellular vesicles carrying miR‐1228‐3p promote chemoresistance via targeting PLAC8 and activating the PI3K/AKT pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nConversely, in gastric cancer miR‐1228 appears to act as a tumor suppressor. One study found that down‐regulation of the miR‐1228* strand was associated with increased NF‐κB activity and epithelial–mesenchymal transition, and restoration of its expression suppressed xenograft tumor formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In another gastric cancer model, enforced expression of miR‐1228 downregulated macrophage migration inhibitory factor (MIF), resulting in cell cycle arrest and reduced angiogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Additional work has demonstrated that exosomes derived from bone marrow mesenchymal stem cells can deliver miR‐1228 to gastric cancer cells, thereby suppressing MMP‐14 expression and inhibiting tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Moreover, in diabetic nephropathy, reduced miR‐1228‐3p levels in kidney biopsies and urine correlate with fibrosis, underscoring its potential as a noninvasive biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer, miR‐1228 contributes to the regulation of normal cellular processes. In human osteoblasts, treatment with 1,25‐dihydroxyvitamin D coinduces miR‐1228 alongside its host gene LRP1, which in turn posttranscriptionally downregulates BMP2K to mediate differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Furthermore, miR‐1228 exhibits anti‐apoptotic properties; its overexpression reduces MOAP1 expression and delays stress‐induced apoptosis, and in alveolar epithelial cells, miR‐1228 overexpression can rescue cells from PM2.5‐induced mitochondrial dysfunction and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " In high glucose–damaged human renal proximal tubule cells, emerging data implicate miR‐1228 as a modulator of cellular injury responses"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", and preliminary evidence in colon cancer suggests that miR‐1228 may regulate tumor proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies underscore the context‐dependent roles of miR‐1228, functioning either as an oncogene or as a tumor suppressor, and influencing cell survival, migration, invasion, and differentiation. This multifaceted microRNA therefore represents a promising target for therapeutic intervention as well as a potential biomarker for disease diagnosis and prognosis.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Daishi Chen, Wei Ma, Zhaoyang Ke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircRNA hsa_circ_100395 regulates miR-1228/TCF21 pathway to inhibit lung cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2018.1515553"}], "href": "https://doi.org/10.1080/15384101.2018.1515553"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30176158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30176158"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jie Hu, Zheng Wang, Bo-Yi Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human miR-1228 as a stable endogenous control for the quantification of circulating microRNAs in cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.28757"}], "href": "https://doi.org/10.1002/ijc.28757"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24488924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24488924"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jian-Wei Wang, Xiao-Feng Wu, Xiao-Juan Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal miR-1228 From Cancer-Associated Fibroblasts Promotes Cell Migration and Invasion of Osteosarcoma by Directly Targeting SCAI."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/096504018X15336368805108"}], "href": "https://doi.org/10.3727/096504018X15336368805108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30180920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30180920"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Luoqiang Lin, Dan Liu, Hongyan Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-1228 promotes breast cancer cell growth and metastasis through targeting SCAI protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Exp Pathol (2015)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26261546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26261546"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Meiheban Bazhabayi, Xingsheng Qiu, Xing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircGFRA1 facilitates the malignant progression of HER-2-positive breast cancer via acting as a sponge of miR-1228 and enhancing AIFM2 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.16963"}], "href": "https://doi.org/10.1111/jcmm.16963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34668628"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34668628"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yanling Bu, Qiang Li, Xiao Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ultrasound-Targeted Microbubble Destruction-Mediated miR-1228 Downregulation Suppresses Tumor Proliferation, Migration, and Invasion of Cervical-Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gynecol Obstet Invest (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000525594"}], "href": "https://doi.org/10.1159/000525594"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35728571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35728571"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Y Zhang, J Dai, H Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-1228 promotes the proliferation and metastasis of hepatoma cells through a p53 forward feedback loop."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/bjc.2014.593"}], "href": "https://doi.org/10.1038/bjc.2014.593"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25422913"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25422913"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yijie Zhang, Qi Pan, Zigong Shao "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular vesicles derived from cancer-associated fibroblasts carry tumor-promotive microRNA-1228-3p to enhance the resistance of hepatocellular carcinoma cells to sorafenib."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-022-00800-7"}], "href": "https://doi.org/10.1007/s13577-022-00800-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36424471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36424471"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Litao Jia, Jia Wu, Lu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Restoration of miR-1228* expression suppresses epithelial-mesenchymal transition in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0058637"}], "href": "https://doi.org/10.1371/journal.pone.0058637"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23554909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23554909"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Litao Jia, Jiamin Chen, Chuangao Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "microRNA-1228"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "⁎"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " impairs the pro-angiogenic activity of gastric cancer cells by targeting macrophage migration inhibitory factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lfs.2017.04.023"}], "href": "https://doi.org/10.1016/j.lfs.2017.04.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28465246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28465246"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Danli Zhong, Chanyuan Wu, Dong Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma-Derived Exosomal hsa-miR-4488 and hsa-miR-1228-5p: Novel Biomarkers for Dermatomyositis-Associated Interstitial Lung Disease with Anti-Melanoma Differentiation-Associated Protein 5 Antibody-Positive Subset."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/6676107"}], "href": "https://doi.org/10.1155/2021/6676107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34368354"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34368354"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Lili Chang, He Gao, Li Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomes derived from miR-1228 overexpressing bone marrow-mesenchymal stem cells promote growth of gastric cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.202878"}], "href": "https://doi.org/10.18632/aging.202878"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33883305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33883305"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Francesca Conserva, Mariagrazia Barozzino, Francesco Pesce, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Urinary miRNA-27b-3p and miRNA-1228-3p correlate with the progression of Kidney Fibrosis in Diabetic Nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-47778-1"}], "href": "https://doi.org/10.1038/s41598-019-47778-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31388051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31388051"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Thomas S Lisse, Rene F Chun, Sandra Rieger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vitamin D activation of functionally distinct regulatory miRNAs in primary human osteoblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbmr.1882"}], "href": "https://doi.org/10.1002/jbmr.1882"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23362149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23362149"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Biao Yan, Jin-liang Zhao "}, {"type": "b", "children": [{"type": "t", "text": "miR-1228 prevents cellular apoptosis through targeting of MOAP1 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Apoptosis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10495-012-0710-9"}], "href": "https://doi.org/10.1007/s10495-012-0710-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22434376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22434376"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Xiaobo Li, Zhen Ding, Chengcheng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-1228(*) inhibit apoptosis in A549 cells exposed to fine particulate matter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Sci Pollut Res Int (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11356-016-6253-9"}], "href": "https://doi.org/10.1007/s11356-016-6253-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26867688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26867688"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Taoran Mo, Qiang Fu, Xiaoyang Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA 1228 Mediates the Viability of High Glucose-Cultured Renal Tubule Cells through Targeting Thrombospondin 2 and PI3K/AKT Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Blood Press Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000516791"}], "href": "https://doi.org/10.1159/000516791"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34784607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34784607"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Sergiu Pasca, Calin Ionescu, David Andras, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating microRNA-194 and microRNA-1228 Could Predict Colon Cancer Proliferation via Phospho S6 Modulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gastrointestin Liver Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15403/jgld-2558"}], "href": "https://doi.org/10.15403/jgld-2558"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32919420"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32919420"}]}]}]}