{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed an oncogenic role for miR-633 in gastric cancer. In gastric cancer tissue and cell lines, miR-633 is highly upregulated and is associated with chemoresistance to agents such as doxorubicin and cisplatin. Mechanistically, miR-633 targets FADD (Fas-associated protein with death domain) to block apoptosis, thereby promoting tumor cell survival and resistance to chemotherapy. Notably, the transcription factor Foxo3a, which accumulates in the nucleus upon doxorubicin treatment, directly represses miR-633 transcription, suggesting a dynamic interplay between chemotherapeutic stress and miR-633 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a different pathological context, miR-633 expression in CD4⁺ T cells from patients with systemic lupus erythematosus (SLE) is significantly reduced. Although mechanistic details remain to be fully elucidated, this finding implies that miR-633 may also play an important role in immune cell regulation, possibly through pathways such as AKT/mTOR that are critical for T cell activation in SLE."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, these findings underscore the context-dependent functions of miR-633: while its overexpression in gastric cancer contributes to chemoresistance by inhibiting apoptotic signaling, its downregulation in SLE may reflect altered immune regulation. These insights into the miR-633/FADD axis and its transcriptional control by Foxo3a highlight potential avenues for therapeutic intervention in both oncologic and autoimmune disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xin Pang, Zhixia Zhou, Zhuang Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Foxo3a-dependent miR-633 regulates chemotherapeutic sensitivity in gastric cancer by targeting Fas-associated death domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2019.1565665"}], "href": "https://doi.org/10.1080/15476286.2019.1565665"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30628514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30628514"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S Chen, Y Wang, H Qin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of miR-633 activated AKT/mTOR pathway by targeting AKT1 in lupus CD4"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lupus (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0961203319829853"}], "href": "https://doi.org/10.1177/0961203319829853"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30760089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30760089"}]}]}]}