NUTM2A-AS1 as a potential key regulator in cancer: unraveling its ceRNA networks and impact on tumor biology.

Abstract

NUTM2A-AS1 is an emerging long noncoding RNA (lncRNA) that has garnered significant attention due to its multifaceted roles in cancer biology. As a member of the ceRNA network, NUTM2A-AS1 modulates gene expression by sequestering microRNAs, thereby influencing key oncogenic pathways. This review aims to provide a comprehensive overview of the current understanding of NUTM2A-AS1 in the development, progression, and metastasis of various cancers, including gastric cancer, hepatocellular carcinoma, neuroblastoma, colorectal cancer, glioma, lung adenocarcinoma, prostate cancer, and renal cell carcinoma. A systematic evaluation of experimental, clinical, and bioinformatics studies was conducted, with an emphasis on studies reporting expression patterns, mechanistic insights, and clinical correlations. Key findings reveal that in gastric cancer, NUTM2A-AS1 functions as a ceRNA for miR‑376a, leading to upregulation of TET1 and HIF-1A and subsequent increase in PD-L1 expression, while also modulating matrine resistance via the miR‑613/ROS/VEGFA axis. In hepatocellular carcinoma, it sponges miR‑186‑5p, thereby derepressing KLF7 and activating the Wnt/β catenin pathway. Neuroblastoma studies demonstrate that NUTM2A-AS1 enhances chemoresistance and metastasis through stabilization of B7-H3, mediated by NR1D1. In colorectal cancer, its transcriptional activation by H3K27 acetylation enables it to sequester miR-126-5p and upregulate FAM3C. Similar ceRNA-driven mechanisms involving miR-376a-3p/YAP1 in glioma, miR-590-5p/METTL3 in lung adenocarcinoma, and miR-376a-3p/PRMT5 in prostate cancer further underscore its oncogenic potential. In addition, NUTM2A-AS1 is incorporated into prognostic lncRNA signatures for renal cell carcinoma. The clinical implications of these findings are significant, as NUTM2A-AS1 holds promise as a biomarker for cancer diagnosis and prognosis and as a target for novel therapeutic strategies. Future research should prioritize in vivo studies and clinical trials, leveraging emerging technologies such as CRISPR and single-cell RNA sequencing, to fully elucidate the therapeutic potential of targeting NUTM2A-AS1 in personalized cancer treatment.