{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have highlighted the multifaceted roles of miR-105 in cancer–host interactions. In breast cancer, miR-105 is secreted within extracellular vesicles following MYC induction and is delivered to stromal fibroblasts, where it reprograms metabolic activity. Such reprogramming enables cancer‐associated fibroblasts to enhance nutrient uptake when resources are abundant and to detoxify metabolic wastes under nutrient‐poor conditions. In an independent study, miR-105 delivered by cancer-cell–derived vesicles was shown to suppress mTOR signaling in both normal and cancer-associated fibroblasts via targeting RAGC, thereby globally reducing mRNA translation and shifting protein synthesis priorities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a variety of solid tumors—including hepatocellular carcinoma, prostate, gastric, esophageal, ovarian and even a subtype of breast cancer—miR-105 expression is frequently downregulated, a change that is associated with enhanced proliferation, invasion, and poorer clinical outcomes. Restoration of miR-105 levels suppresses tumor growth through different mechanisms: in hepatocellular carcinoma it deactivates the PI3K/AKT pathway and directly downregulates targets such as insulin receptor substrate-1, PDK1 and AKT1, leading to increased expression of cell cycle inhibitors; in prostate cancer, overexpression of miR-105 targets CDK6 to reduce cell proliferation; in gastric cancer, miR-105-5p directly suppresses PD-L1 expression to reduce immune evasion, while other studies in gastric and esophageal cancers further implicate its regulatory influence on molecules such as SOX9 and additional oncogenic mediators; and in ovarian carcinoma, reduced miR-105 is linked to chemoresistance with functional studies showing its ability to potentiate sensitivity to paclitaxel or cisplatin."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in tumor biology, miR-105 has emerged as an important regulator of differentiation and cellular signaling in diverse contexts. In primitive and definitive hematopoiesis, miR-105 enhances megakaryocyte production from common myeloid progenitors via direct targeting of the transcription factor c-Myb. In the context of cartilage homeostasis, miR-105 is downregulated by FGF2‐induced mechanisms, which in turn leads to derepression of Runx2 and subsequent upregulation of proteases (ADAMTS family) that destruct extracellular matrix components—a process implicated in osteoarthritis pathogenesis. Moreover, miR-105 has been linked to the modulation of SOX9 during osteogenic differentiation of adipose-derived mesenchymal stem cells and is involved in regulatory axes in glioma (through WEE1) and osteosarcoma (via FOXO1), while exosomal miR-105-5p derived from bladder cancer stem cells promotes malignancy by targeting GPR12."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Yan, Xiwei Wu, Weiying Zhou, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of miRNA-105 inhibits the progression of gastric carcinoma by directly targeting SOX9."}]}, {"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_201905_17804"}], "href": "https://doi.org/10.26355/eurrev_201905_17804"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31115004"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31115004"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ruixiang Gao, Zhen Wang, Qiang Liu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Role of hsa‑miR‑105 during the pathogenesis of paclitaxel resistance and its clinical implication in ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2021.8035"}], "href": "https://doi.org/10.3892/or.2021.8035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33846814"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33846814"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Christos Miliotis, Frank J Slack "}, {"type": "b", "children": [{"type": "t", "text": "miR-105-5p regulates PD-L1 expression and tumor immunogenicity in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2021.05.037"}], "href": "https://doi.org/10.1016/j.canlet.2021.05.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34098061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34098061"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Viraj Kamat, Prasuna Paluru, Melissa Myint, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA screen of human embryonic stem cell differentiation reveals miR-105 as an enhancer of megakaryopoiesis from adult CD34+ cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/stem.1640"}], "href": "https://doi.org/10.1002/stem.1640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24446170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24446170"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Quanbo Ji, Xiaojie Xu, Yameng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-105/Runx2 axis mediates FGF2-induced ADAMTS expression in osteoarthritis cartilage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Med (Berl) (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00109-016-1380-9"}], "href": "https://doi.org/10.1007/s00109-016-1380-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26816250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26816250"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "J-C Shang, G-Z Yu, Z-W Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-105 inhibits gastric cancer cells metastasis, epithelial-mesenchymal transition by targeting SOX9."}]}, {"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_201907_18429"}], "href": "https://doi.org/10.26355/eurrev_201907_18429"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31364116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31364116"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "S-T Suo, P Gong, X-J Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of long non-coding RNA VIM-AS1 inhibits glioma cell proliferation and migration, and increases the cell apoptosis via modulation of WEE1 targeted by miR-105-5p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202006_21673"}], "href": "https://doi.org/10.26355/eurrev_202006_21673"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32633376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32633376"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Chun-Liang Li, Kai Wang, Zhao-Wei Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-105 enhances osteogenic differentiation of hADSCs via the targeted regulation of SOX9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tissue Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tice.2021.101540"}], "href": "https://doi.org/10.1016/j.tice.2021.101540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33838353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33838353"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Gaojian Pan, Bo Jiang, Zhongquan Yi, et al. 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