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MT1JP:一种关键的肿瘤抑制长链非编码RNA及其在癌症进展中的作用和治疗潜力

MT1JP: A Pivotal Tumor-Suppressing LncRNA and its Role in Cancer Progression and Therapeutic Potential.

作者信息

He Haodong, Yang Jingjie, Peng Wenjin, Li Moyu, Shuai Meiyan, Tan Faming, Cao Zheng, Yuan Chengfu

机构信息

Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.

College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.

出版信息

Curr Drug Targets. 2025;26(6):394-409. doi: 10.2174/0113894501365982250119150404.

Abstract

Metallothionein 1J pseudogene (MT1JP) is a long non-coding RNA (lncRNA) that functions as a tumor suppressor in various malignancies. Reduced MT1JP expression is associated with increased tumor proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and treatment resistance in nine cancers, such as gastric cancer, intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and breast cancer. Mechanistically, MT1JP acts as a competitive endogenous RNA (ceRNA) to regulate oncogenic microRNAs (miRNAs), including miR-92a-3p, miR-214-3p, and miR-24-3p. This regulation restores tumor suppressor genes, such as FBXW7, RUNX3, and PTEN, thereby disrupting oncogenic pathways, including PI3K/AKT, Wnt/β- catenin, and p53, promoting apoptosis, and inhibiting tumor progression. Clinically, MT1JP expression correlates with tumor grade, differentiation, TNM stage, lymph node metastasis, and patient prognosis, suggesting its potential as a diagnostic and prognostic biomarker. Furthermore, its therapeutic potential in RNA-based treatments has attracted significant attention. Despite these findings, questions remain regarding its role in epigenetic regulation, transcriptional control, and RNA delivery. This review explores the molecular mechanisms underlying MT1JP, highlighting its clinical relevance and potential as a therapeutic target. Future research should focus on elucidating its role in epigenetic regulation, overcoming challenges in therapeutic delivery, and validating its utility as a biomarker for different cancers. MT1JP holds promise for advancing precision oncology by providing innovative approaches for cancer diagnosis and treatment.

摘要

金属硫蛋白1J假基因(MT1JP)是一种长链非编码RNA(lncRNA),在多种恶性肿瘤中发挥肿瘤抑制作用。MT1JP表达降低与胃癌、肝内胆管癌、肝细胞癌和乳腺癌等九种癌症的肿瘤增殖、迁移、侵袭、上皮-间质转化(EMT)及治疗抵抗增加相关。机制上,MT1JP作为竞争性内源性RNA(ceRNA)调节致癌性微小RNA(miRNA),包括miR-92a-3p、miR-214-3p和miR-24-3p。这种调节可恢复肿瘤抑制基因,如FBXW7、RUNX3和PTEN,从而破坏致癌途径,包括PI3K/AKT、Wnt/β-连环蛋白和p53途径,促进细胞凋亡并抑制肿瘤进展。临床上,MT1JP表达与肿瘤分级、分化、TNM分期、淋巴结转移及患者预后相关,提示其作为诊断和预后生物标志物的潜力。此外,其在基于RNA的治疗中的治疗潜力已引起广泛关注。尽管有这些发现,但关于其在表观遗传调控、转录控制和RNA递送中的作用仍存在疑问。本综述探讨了MT1JP的分子机制,强调了其临床相关性及作为治疗靶点的潜力。未来研究应聚焦于阐明其在表观遗传调控中的作用,克服治疗递送中的挑战,并验证其作为不同癌症生物标志物的效用。MT1JP有望通过提供癌症诊断和治疗的创新方法推动精准肿瘤学发展。

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