Xia Yuyang, Pei Tianjiao, Zhao Junjie, Wang Zilin, Shen Yu, Yang Yang, Liang Jiayu
Department of Urology, Institute of Urology, West China Hospital, West China School of Medicine, Sichuan University, 610041, Chengdu, China.
Department of Reproductive Medicine, West China Second University Hospital of Sichuan University, Chengdu, China.
Cell Death Discov. 2024 Feb 14;10(1):76. doi: 10.1038/s41420-024-01832-8.
Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs with transcript lengths of >200 nucleotides. Mounting evidence suggests that lncRNAs are closely associated with tumorigenesis. LncRNA H19 (H19) was the first lncRNA to function as an oncogene in many malignant tumors. Apart from the established role of H19 in promoting cell growth, proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and metastasis, it has been recently discovered that H19 also inhibits programmed cell death (PCD) of cancer cells. In this review, we summarize the mechanisms by which H19 regulates PCD in cancer cells through various signaling pathways, molecular mechanisms, and epigenetic modifications. H19 regulates PCD through the Wnt/β-catenin pathway and the PI3K-Akt-mTOR pathway. It also acts as a competitive endogenous RNA (ceRNA) in PCD regulation. The interaction between H19 and RNA-binding proteins (RBP) regulates apoptosis in cancer. Moreover, epigenetic modifications, including DNA and RNA methylation and histone modifications, are also involved in H19-associated PCD regulation. In conclusion, we summarize the role of H19 signaling via PCD in cancer chemoresistance, highlighting the promising research significance of H19 as a therapeutic target. We hope that our study will contribute to a broader understanding of H19 in cancer development and treatment.
长链非编码RNA（lncRNAs）是一类转录长度大于200个核苷酸的非编码RNA。越来越多的证据表明，lncRNAs与肿瘤发生密切相关。LncRNA H19（H19）是首个在许多恶性肿瘤中发挥癌基因作用的lncRNA。除了在促进细胞生长、增殖、侵袭、迁移、上皮-间质转化（EMT）和转移方面已确立的作用外，最近还发现H19也抑制癌细胞的程序性细胞死亡（PCD）。在本综述中，我们总结了H19通过各种信号通路、分子机制和表观遗传修饰来调节癌细胞中PCD的机制。H19通过Wnt/β-连环蛋白途径和PI3K-Akt-mTOR途径调节PCD。它在PCD调节中还作为竞争性内源性RNA（ceRNA）发挥作用。H19与RNA结合蛋白（RBP）之间的相互作用调节癌症中的细胞凋亡。此外，表观遗传修饰，包括DNA和RNA甲基化以及组蛋白修饰，也参与了与H19相关的PCD调节。总之，我们总结了H19通过PCD信号在癌症化疗耐药中的作用，突出了H19作为治疗靶点的有前景的研究意义。我们希望我们的研究将有助于更广泛地理解H19在癌症发展和治疗中的作用。
