{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies in colorectal cancer have revealed that miR‑3140 normally functions as an inhibitor of the autophagy pathway, thereby reducing cell viability, migration, and invasion while promoting apoptosis under hypoxic conditions. In this context, circCCDC66 acts as a molecular sponge for miR‑3140, sequestering it and consequently relieving its suppressive effects on autophagy. This regulatory mechanism facilitates the progression of hypoxia‐exposed colorectal cancer cells, suggesting that modulating miR‑3140 activity could represent a novel therapeutic strategy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Disparate from the role of miR‑3140 in cancer progression, structural investigations into the tweety homolog (TTYH) family elucidated a unique fold and Ca2+‑dependent quaternary organization of TTYH2 and TTYH3. These studies, while not addressing miR‑3140, provide insight into Ca2+‑regulated protein interactions, membrane‐spanning dimers, and potential roles in cell adhesion and developmental signaling. Such mechanistic insights into TTYH structure contribute to our growing understanding of the diverse molecular pathways that converge on processes like cellular migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "Collectively, these findings underscore the multifaceted nature of cellular regulation in both cancer and normal physiology. While miR‑3140’s suppression of autophagy is a critical factor in hypoxic colorectal cancer cell survival and invasiveness, complementary studies on membrane proteins such as TTYHs expand our overall grasp of calcium‐mediated cellular mechanisms that could intersect with miRNA regulatory networks. Ongoing research integrating these diverse molecular insights promises to enhance future therapeutic strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jin Feng, Zhong Li, Ling Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2020.4747"}], "href": "https://doi.org/10.3892/ijmm.2020.4747"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33125087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33125087"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Baobin Li, Christopher M Hoel, Stephen G Brohawn "}, {"type": "b", "children": [{"type": "t", "text": "Structures of tweety homolog proteins TTYH2 and TTYH3 reveal a Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-dependent switch from intra- to intermembrane dimerization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-27283-8"}], "href": "https://doi.org/10.1038/s41467-021-27283-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34824283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34824283"}]}]}]}