Department of Hematology, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, Guangdong, China.
J Hematol Oncol. 2020 Dec 2;13(1):163. doi: 10.1186/s13045-020-01002-0.
To survive, cancer cells are subjected to various internal and external adverse factors, including genetic mutations, hypoxia, nutritional deficiencies, and drug toxicity. All of these factors result in the accumulation of unfolded proteins in the endoplasmic reticulum, which leads to a condition termed endoplasmic reticulum stress (ER stress) and triggers the unfolded protein response (UPR). UPR downstream components strictly control transcription and translation reprogramming to ensure selective gene expression, including that of non-coding RNA (ncRNAs), to adapt to adverse environments. NcRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play important roles in regulating target gene expression and protein translation, and their aberrant expression is related to tumor development. Dysregulation of ncRNAs is involved in the regulation of various cellular characteristics of cancer cells, including growth, apoptosis, metastasis, angiogenesis, drug sensitivity, and tumor stem cell properties. Notably, ncRNAs and ER stress can regulate each other and collaborate to determine the fate of tumor cells. Therefore, investigating the interaction between ER stress and ncRNAs is crucial for developing effective cancer treatment and prevention strategies. In this review, we summarize the ER stress-triggered UPR signaling pathways involved in carcinogenesis followed by the mutual regulation of ER stress and ncRNAs in cancer, which provide further insights into the understanding of tumorigenesis and therapeutic strategies.
为了生存，癌细胞会受到各种内外源不良因素的影响，包括基因突变、缺氧、营养缺乏和药物毒性。所有这些因素都会导致内质网中未折叠蛋白的积累，从而导致内质网应激（ER 应激），并触发未折叠蛋白反应（UPR）。UPR 下游成分严格控制转录和翻译重编程，以确保选择性基因表达，包括非编码 RNA（ncRNA）的表达，从而适应不利的环境。ncRNA，包括 microRNAs（miRNAs）、长链非编码 RNA（lncRNAs）和环状 RNA（circRNAs），在调节靶基因表达和蛋白翻译方面发挥着重要作用，其异常表达与肿瘤的发生发展有关。ncRNA 的失调参与调节癌细胞的各种细胞特性，包括生长、凋亡、转移、血管生成、药物敏感性和肿瘤干细胞特性。值得注意的是，ncRNA 和 ER 应激可以相互调节并协同作用，决定肿瘤细胞的命运。因此，研究 ER 应激与 ncRNA 之间的相互作用对于开发有效的癌症治疗和预防策略至关重要。在这篇综述中，我们总结了 ER 应激触发的致癌作用中的 UPR 信号通路，以及 ER 应激与 ncRNA 在癌症中的相互调节，这为进一步了解肿瘤发生和治疗策略提供了新的见解。
