{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐650 (miR-650) is emerging as a key regulator in several gastrointestinal and hematologic malignancies. In gastric cancer, it is overexpressed and promotes tumorigenesis and metastasis by directly targeting tumor suppressors such as ING4 (20381459) and, in addition, is upregulated in Helicobacter pylori–positive tumors where it represses LATS2 to favor oncogenic signaling (33147052). In colorectal cancer, miR-650 contributes to tumor progression by downregulating NDRG2 through mechanisms that involve transcriptional as well as epigenetic control (21352815). In chronic lymphocytic leukemia, its expression is intrinsically coupled with its host immunoglobulin lambda gene and appears to control key cell cycle and survival regulators like CDK1, ING4, and EBF3, with higher levels being associated with a favorable prognosis (22234685). Conversely, while its role in hepatocellular carcinoma remains unsettled in one study (22767438), additional evidence indicates that miR-650 can fuel malignant behavior in other contexts by modulating similar molecular targets."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a broad spectrum of solid tumors, miR-650 exerts diverse functions that can either promote or inhibit tumor aggressiveness depending on the cellular context. In lung adenocarcinoma, elevated miR-650 levels are associated with enhanced metastasis and chemoresistance to docetaxel through suppression of ING4 (23991130). In prostate cancer, upregulation of miR-650 suppresses the tumor suppressor CSR1, thereby facilitating cell cycle progression and tumor growth (25956032). In glioma, increased miR-650 expression correlates with higher malignancy and poorer prognosis, and in a separate study, it represses proliferation by targeting FAM83F (24062138, 30556880). Moreover, in acute myeloid leukemia, miR-650 may significantly contribute to disease progression (28574132). In breast cancer, amplification of the chromosomal region containing miR-650 has been linked to epithelial-to-mesenchymal transition (EMT) and an aggressive phenotype, with bioinformatic analyses implicating downstream targets such as STAT5A (28101578, 33086498). In contrast, ovarian cancer appears to behave differently, as miR-650 is downregulated and its restoration decreases cell viability, migration, and invasion through the targeting of KLF12 (36272152)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "14"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic and tumor-suppressive roles in cancer, miR-650 also plays significant roles in non-neoplastic processes and immune regulation. In primary human monocyte-derived dendritic cells, downregulation of miR-650 upon pathogen stimulation relieves repression on interferon-stimulated genes, thereby bolstering antiviral responses (26460926). In the context of inflammatory diseases, investigation into rheumatoid arthritis synovial fibroblasts is shedding light on its potential impact on cell proliferation, migration, invasion, and apoptosis (28129626). Moreover, in ulcerative colitis, overexpression of miR-650 exacerbates mucosal inflammation by promoting apoptosis via targeting NLRP6 (31399193), and in acute renal allograft rejection, elevated miR-650 contributes to apoptotic and inflammatory events by suppressing BCL11B (29039465). Plasma levels of miR-650 have also been correlated with cognitive function in Alzheimer’s disease, suggesting a broader relevance in neurodegenerative disorders (31556571)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "19"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "XueLi Zhang, WeiYing Zhu, JiFa Zhang, et al. 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