{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTTN‐AS1 is a long noncoding RNA whose aberrant expression is frequently observed in a broad range of malignancies, including esophageal squamous cell carcinoma, cervical cancer, papillary thyroid cancer, gastric cancer, lung adenocarcinoma, prostate cancer, cholangiocarcinoma, skin cutaneous melanoma, triple‐negative breast cancer, hepatocellular carcinoma, oral squamous cell carcinoma, and pancreatic cancer. In these cancers, TTN‐AS1 is typically upregulated and associated with advanced clinical stage, enhanced proliferation, migration, invasion, epithelial–mesenchymal transition, and metastasis that ultimately portend poor patient prognosis. Mechanistically, TTN‐AS1 generally functions as an oncogenic competing endogenous RNA by sponging a variety of tumor‐suppressive microRNAs (e.g., miR‐133b, miR‐142‐5p, miR‐573, miR‐320a, miR‐376b‐3p, miR‐139‐5p, miR‐199a‐3p, and miR‐513a‐5p), thereby modulating the expression of numerous key oncogenic effectors—including transcription factors, cell cycle regulators, and mediators of EMT (such as Snail1, FSCN1, CDK5, E2F3, neuropilin‐1, KLF12, PTEN, SPOCK1, PAK3, RUNX1, SFN, and SQLE)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, TTN‐AS1 exhibits context‐dependent behavior in certain cancers. For example, in ovarian cancer, TTN‐AS1 expression is downregulated, and its overexpression suppresses tumor proliferation and colony formation while promoting apoptosis through a mechanism involving the miR‐15b‐5p/FBXW7 axis. Moreover, in large intestine cancer, TTN‐AS1 is induced following radiation exposure and contributes to radioresistance by downregulating miR‐134‐5p, which leads to increased levels of PAK3 and P21 and activation of the AKT/GSK‐3β/β‐catenin pathway. Preliminary investigations in gallbladder carcinoma also implicate TTN‐AS1 in tumor progression, and a meta‐analysis consolidates its overall prognostic significance across diverse malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence further expands the functional repertoire of TTN‐AS1. In skin cutaneous melanoma, TTN‐AS1 facilitates tumorigenesis and metastasis by epigenetically upregulating its sense transcript, TTN, through both enhanced promoter activity and increased mRNA stability. In addition, TTN‐AS1 can be preferentially sorted into exosomes, suggesting a role in mediating intercellular communication within the tumor microenvironment. Collectively, these multifaceted, context‐dependent functions underscore the potential of targeting the TTN‐AS1/miRNA/target regulatory axis as a promising diagnostic and therapeutic strategy in cancer management."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chenyu Lin, Shengnan Zhang, Ying Wang, et al. 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