{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IRAIN is a long noncoding RNA that is transcribed antisense from an intronic promoter within the IGF1R locus and plays an important role in modulating chromatin architecture and gene expression. In several hematopoietic malignancies such as acute myeloid leukemia and breast cancer, IRAIN is typically expressed in a monoallelic (paternal) and imprinted manner, where it engages in long‐range chromosomal interactions – for example, facilitating the formation of an enhancer/promoter loop at the IGF1R locus – to regulate IGF1R transcription and downstream signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In contexts such as glioma, laryngeal carcinoma and multiple myeloma, IRAIN appears to act as a tumor suppressor by inhibiting proliferation, migration, and resistance to therapy through inactivation of the IGF-1R/PI3K-NF-κB pathway or by maintaining proper allele-specific expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Conversely, in non–small cell lung cancer and pancreatic cancer, IRAIN is reported to be upregulated where it functions as an oncogenic factor by promoting cell growth and inhibiting apoptosis, with its elevated expression correlating with adverse clinicopathological features."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, innovative therapeutic strategies have emerged that aim to restore the aberrant IGF1R/IRAIN balance – for instance, by harnessing an antisense lncRNA–mediated intragenic cis competition approach to suppress IGF1R signaling – highlighting the potential of IRAIN as both a diagnostic biomarker and a target for precision therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jingnan Sun, Wei Li, Yunpeng Sun, et al. 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