{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have uncovered that the long non‑coding RNA "}, {"type": "b", "children": [{"type": "t", "text": "LIFR‑AS1"}]}, {"type": "t", "text": " plays versatile and context‐dependent roles in human diseases by modulating key cellular processes such as proliferation, apoptosis, migration, invasion, and treatment resistance. In colorectal cancer, for instance, LIFR‑AS1 functions as a competitive endogenous RNA (ceRNA) by sponging miR‑29a, thereby relieving its repression on TNFAIP3 expression and modulating resistance to photodynamic therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In glioma, LIFR‑AS1 is expressed at low levels, and its overexpression suppresses cell proliferation, migration, invasion, and chemoresistance to temozolomide via regulation of the miR‑4262/NF‑κB signaling pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Similar tumor‐suppressive roles have been observed in papillary thyroid carcinoma and gastric carcinoma, where LIFR‑AS1 overexpression impairs tumorigenesis by modulating axes such as miR‑31‑5p/SIDT2"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and miR‑4698/MTUS1, leading to inhibition of the MEK/ERK pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, other investigations in gastric cancer and clear cell kidney carcinoma have reported that elevated LIFR‑AS1 expression correlates with larger tumor size, lymphatic metastasis, and poor clinical outcomes, suggesting an oncogenic function in these contexts"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In osteosarcoma, macrophage‑derived exosomal LIFR‑AS1 enhances tumor progression by sponging miR‑29a and modulating the NFIA axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, studies in non‑small cell lung cancer and breast cancer have shown that downregulation of LIFR‑AS1 is associated with increased migration, invasion, and metastasis. In these malignancies, LIFR‑AS1 exerts tumor‑suppressive effects by sponging miR‑942‑5p to derepress targets such as ZNF471 and by affecting other downstream molecules"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond cancer, genetic variations in the LIFR‑AS1 locus have been linked to non‑malignant conditions. For example, polymorphisms related to LIFR‑AS1 have been associated with increased risk of preterm birth and larger uterine fibroid size, possibly through modulation of leukemia inhibitory factor (LIF) signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, integrative bioinformatics analyses have incorporated LIFR‑AS1 into broader ceRNA networks in colorectal and breast cancers, further underscoring its potential as an independent prognostic biomarker and a therapeutic target"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight the multifaceted role of LIFR‑AS1 in regulating oncogenic and tumor‐suppressive pathways depending on cellular context. Its ability to act as a ceRNA and modulate key molecular axes not only influences tumor behavior and treatment response but also extends to the regulation of non‑cancerous conditions, positioning LIFR‑AS1 as a promising candidate for future diagnostic and therapeutic strategies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kuijie Liu, Hongliang Yao, Yu Wen, et al. 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