{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that miR‑1229, including its mature isoform miR‑1229‑3p, is up‑regulated in several human cancers and functions predominantly as an oncogenic microRNA. In colorectal cancer, elevated circulating exosomal miR‑1229 levels correlate with tumor size, lymphatic metastasis, advanced stage and poor survival, acting in part through suppression of HIPK2 to activate the VEGF pathway and promote angiogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, in breast cancer, increased miR‑1229 expression stimulates malignant cell proliferation via activation of the Wnt/β‑catenin signaling cascade—achieved by targeting multiple negative regulators such as APC, GSK‑3β and ICAT—while in head and neck squamous cell carcinoma and hepatocellular carcinoma, miR‑1229‑3p overexpression is associated with enhanced tumor progression and serves as an independent prognostic marker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " In addition, the diagnostic potential of circulating miR‑1229 has been demonstrated in colorectal cancer, further emphasizing its clinical relevance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nmiR‑1229‑3p is also a pivotal downstream effector in competing endogenous RNA networks. For instance, in glioma, the oncogenic role of miR‑1229‑3p is unleashed when its activity is de‑repressed by the sponging activity of circ_0037251, resulting in the up‑regulation of mTOR and increased tumor aggressiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Similarly, in breast cancer, the tumor‑suppressive circ_0000442 exerts its function by binding miR‑1229‑3p, which in turn leads to an increase in ZBTB1 expression and inhibition of malignant behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " A comparable mechanism has been observed in gastric cancer, where decreased levels of circ_0005758 result in miR‑1229‑3p‑mediated down‑regulation of GCNT4, thereby promoting oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncogenesis, the structure and processing of pre‑miR‑1229 have been implicated in Alzheimer’s disease pathology. A disease‑associated single nucleotide polymorphism in pre‑miR‑1229 shifts the equilibrium between a G‑quadruplex conformation and the canonical hairpin structure, subsequently altering the production of mature miR‑1229‑3p. This change is thought to affect the translation of SORL1, a protein important for amyloid precursor protein processing, and may represent a novel therapeutic avenue in Alzheimer’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhanyao Tan, Haiqing Zheng, Xiangxia Liu, et al. 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