{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn Drosha-deficient gastric cancer cells, the noncanonical miR‐6778‐5p—a Drosha-independent 5′-tail mirtron derived from intron 5 of the SHMT1 gene—has emerged as a critical regulator of cancer stem cell (CSC) maintenance. miR‐6778‐5p acts by targeting YWHAE, which in turn positively regulates its host gene SHMT1, ultimately reinforcing cytoplasmic one‑carbon metabolism. This compensatory activation sustains the malignant stemness and proliferation of gastric cancer cells, particularly when canonical miRNA processing is compromised."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctionally, elevated miR‐6778‐5p levels in Drosha‐silenced cells correlate with enhanced CSC characteristics and resistance to 5‑fluorouracil therapy. Experimental knockdown of miR‐6778‑5p or its downstream effector SHMT1 results in a notable decrease in CSC sphere formation and increased chemosensitivity, highlighting its role in mediating the metabolic shift from mitochondrial SHMT2‐driven pathways to a cytoplasmic SHMT1‐dependent process."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThese findings underscore the potential of miR‐6778‑5p not only as a biomarker for tumor cells with attenuated Drosha expression but also as a promising therapeutic target to overcome chemoresistance in gastric cancer. Further exploration of its regulatory network could offer new insights into the metabolic adaptations driving CSC maintenance and malignancy, providing a basis for novel intervention strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maojia Zhao, Yixuan Hou, Yan-E Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Drosha-independent miR-6778-5p strengthens gastric cancer stem cell stemness via regulation of cytosolic one-carbon folate metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2020.02.040"}], "href": "https://doi.org/10.1016/j.canlet.2020.02.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32142918"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32142918"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mingjun Ren, Li Xing, Wanping Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Drosha-Independent MicroRNA6778-5p/GSK3"}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "β"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Axis Mediates the Proliferation of Gastric Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comput Intell Neurosci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2022/5932512"}], "href": "https://doi.org/10.1155/2022/5932512"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36210981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36210981"}]}]}]}