{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in diverse cancers have revealed that miR‑616 is frequently dysregulated and plays pivotal roles in tumor progression. In prostate cancer, miR‑616 overexpression promotes androgen‑independent proliferation by downregulating TFPI‑2, while in gastric cancer and hepatocellular carcinoma its elevated levels enhance angiogenesis, epithelial‑to‑mesenchymal transition (EMT), migration and invasion—activities that are linked to the suppression of tumor suppressors such as PTEN. Moreover, increased expression of miR‑616 has been implicated in glioma proliferation, ovarian cancer cell migration and EMT via targeting TIMP2, and it even emerges as a novel biomarker in renal cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its oncogenic functions, miR‑616 participates in intricate regulatory networks through competing endogenous RNA (ceRNA) mechanisms. In colorectal cancer, a circular RNA (circRNA) functions as a sponge for a set of miRNAs including miR‑616, thereby modulating the EMT‑inducing transcription factor ZEB1. In breast cancer, upregulation of GLI1 via sequestration of miR‑616‑3p by circ_DCAF6 enhances cell growth and stemness, while a similar ceRNA regulatory axis in acute myeloid leukemia via circSLC25A13‐mediated sponging of miR‑616‑3p promotes disease progression by affecting ADCY2 expression. Beyond cancer, long non‑coding RNAs such as LOC285194 have been shown to sequester miR‑616 in psoriasis, relieving its inhibitory effect on GATA3 and thereby influencing keratinocyte growth. Moreover, altered miR‑616 levels impact complement‑dependent cytotoxicity by modulating the expression of membrane complement regulators (CD46 and CD59), and genetic studies on miR‑binding site single nucleotide polymorphisms (miR‑SNPs) as well as variants in the miR‑616 region have linked this microRNA to cardiovascular conditions such as atherosclerosis, stroke, and premature coronary artery disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUnder conditions of cellular stress, miR‑616 is co‑transcribed with the CHOP gene and is upregulated upon activation of the unfolded protein response via the PERK pathway. In this context, miR‑616 exerts anti‑proliferative effects in breast cancer cells by directly targeting c‑MYC, thereby contributing to ER stress‑induced growth inhibition. In lung epithelial cells, miR‑616‑3p directly targets the 3′‑UTR of the CXCL5 gene, attenuating inflammatory responses by reducing neutrophil chemoattraction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stephanie Ma, Yuen Piu Chan, Pak Shing Kwan, et al. 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