{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐656 (including its isoform miR‐656‐3p) functions predominantly as a tumor suppressor in several cancers. In glioma, miR‐656 is significantly downregulated and exerts its inhibitory effect on tumor progression by directly targeting BMPR1A, thereby suppressing both canonical BMP/Smad and non‐canonical MAPK signaling pathways that drive cell proliferation, neurosphere formation, migration, and invasion. Moreover, as an integral member of the larger miR‐379/miR‐656 (C14MC) cluster, its reduced expression in diffuse gliomas represents an early event in gliomagenesis and is associated with poorer prognosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn hepatocellular carcinoma and melanoma, miR‐656‐3p is functionally inactivated by its sequestration from oncogenic non‐coding RNAs. In HCC, both circBACH1 and the long non‐coding RNA SNHG14 act as competing endogenous RNAs by sponging miR‐656‐3p, which leads to the elevation of targets such as SERBP1 and SIRT5 and thereby promotes cell proliferation, migration, invasion, and epithelial–mesenchymal transition. Similarly, in melanoma, upregulation of lncRNA SNHG8—which is induced by transcription factor YY1—sequesters miR‐656, resulting in increased SERBP1 expression and enhanced malignant behaviors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these cancer types, miR‐656‐3p plays crucial roles in regulating additional malignancies. In colorectal cancer, its knockdown promotes chemoresistance, while its overexpression targets SGPP1 to inhibit growth and epithelial–mesenchymal transition. In nasopharyngeal carcinoma, circ_0028007 sponges miR‐656‐3p, leading to an increase in ELF2 expression and subsequent enhancement of cell growth, migration, invasion, and angiogenesis. In lung cancer, lncRNA SDCBP2‐AS1 impedes miR‐656‐3p function, thereby reducing ferroptosis through upregulation of CRIM1. Lastly, in cervical cancer, hypermethylation‐mediated silencing of the C14MC cluster—including miR‐656—fosters tumor progression by promoting proliferation, migration, invasion, and metabolic reprogramming; reactivation of this cluster mitigates these oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mian Guo, Zhenfeng Jiang, Xiaoming Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-656 inhibits glioma tumorigenesis through repression of BMPR1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgu030"}], "href": "https://doi.org/10.1093/carcin/bgu030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24480809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24480809"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Subhashree Nayak, Meghali Aich, Anupam Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel internal regulators and candidate miRNAs within miR-379/miR-656 miRNA cluster can alter cellular phenotype of human glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-26000-8"}], "href": "https://doi.org/10.1038/s41598-018-26000-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29769662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29769662"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anupam Kumar, Subhashree Nayak, Pankaj Pathak, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "CircRNA circBACH1 (hsa_circ_0061395) serves as a miR-656-3p sponge to facilitate hepatocellular carcinoma progression through increasing SERBP1 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2021.03.136"}], "href": "https://doi.org/10.1016/j.bbrc.2021.03.136"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33831787"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33831787"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Baihui Shan, Shengming Qu, Sha Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "YY1-induced long non-coding RNA small nucleolar RNA host gene 8 promotes the tumorigenesis of melanoma via the microRNA-656-3p/SERPINE1 mRNA binding protein 1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2022.2034586"}], "href": "https://doi.org/10.1080/21655979.2022.2034586"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35156513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35156513"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Baoming Zhang, Shanting Gao, Zengtao Bao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-656-3p inhibits colorectal cancer cell migration, invasion, and chemo-resistance by targeting sphingosine-1-phosphate phosphatase 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2022.2031420"}], "href": "https://doi.org/10.1080/21655979.2022.2031420"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35081855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35081855"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xiaojun Ma, Yan Li "}, {"type": "b", "children": [{"type": "t", "text": "Circ_0028007 Aggravates the Malignancy of Nasopharyngeal Carcinoma by Regulating miR-656-3p/ELF2 Axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Genet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10528-022-10205-8"}], "href": "https://doi.org/10.1007/s10528-022-10205-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35239093"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35239093"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ninghuang Dai, Haitao Ma, Yu Feng "}, {"type": "b", "children": [{"type": "t", "text": "Silencing of long non-coding RNA SDCBP2-AS1/microRNA-656-3p/CRIM1 axis promotes ferroptosis of lung cancer cells."}]}, {"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/2023.69.9.29"}], "href": "https://doi.org/10.14715/cmb/2023.69.9.29"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37807311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37807311"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sriharikrishnaa Srinath, Padacherri Vethil Jishnu, Vinay Koshy Varghese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation and tumor-suppressive function of the miR-379/miR-656 (C14MC) cluster in cervical cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.13611"}], "href": "https://doi.org/10.1002/1878-0261.13611"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38400534"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38400534"}]}]}]}