{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LINC00665 is a multifunctional long non‐coding RNA whose aberrant expression has been reported in a broad range of human malignancies as well as in non‐malignant pathologic contexts. In several tumor types—including lung adenocarcinoma, breast cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, glioma, prostate cancer, and others—LINC00665 is frequently upregulated and correlates with adverse clinical features and poor prognosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " LINC00665 promotes tumor cell proliferation, migration, invasion, angiogenesis, and epithelial-to-mesenchymal transition by modulating key oncogenic signaling cascades (including ERK, NF-κB, PI3K/Akt, and Wnt/β-catenin) and by interacting directly with proteins that regulate stability and transcriptional activity. Mechanistically, it frequently acts as a competing endogenous RNA (ceRNA) that “sponges” tumor-suppressive microRNAs (for example, miR-98, miR-379-5p, miR-138-5p, miR-3619-5p, among others), thereby de-repressing the expression of a variety of oncogenes such as AKR1B10, LIN28B, E2F3, β-catenin, and additional effectors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In some contexts, such as non-small cell lung cancer and gastric cancer, LINC00665 also contributes to chemoresistance by modulating drug-response genes and stress pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Intriguingly, recent work in breast cancer has shown that LINC00665 can encode a functional micropeptide (CIP2A-BP) whose expression is tightly controlled by TGF-β signaling and which modulates tumor metastasis by affecting PI3K/AKT/NFκB signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Beyond its well‐established oncogenic functions, LINC00665 is also implicated in shaping the tumor microenvironment and immune response—as evidenced by its incorporation into ceRNA networks that influence lymphocyte infiltration in conditions such as systemic sclerosis-related interstitial lung disease"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "—and in modulating neurotoxicity induced by agents like bupivacaine."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Overall, this diverse spectrum of molecular functions underscores LINC00665’s potential as both a prognostic biomarker and a promising therapeutic target across multiple human cancers and pathological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhuangzhuang Cong, Yifei Diao, Yang Xu, et al. 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