Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Cell Death Dis. 2024 Mar 29;15(3):236. doi: 10.1038/s41419-024-06607-8.
Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial-mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.
转移是癌症治疗的一个瓶颈。研究表明，长非编码 RNA（lncRNA）在调节癌症转移中起着关键作用；然而，我们对胃癌（GC）中的 lncRNA 的理解仍然有限。对倾向转移的 GC 组织进行 RNA-seq 以揭示与转移相关的 lncRNA，发现上调的小核仁 RNA 宿主基因 26（SNHG26）表达，这预示着 GC 患者预后不良。功能实验表明，SNHG26 促进了细胞上皮-间充质转化和体外及体内的增殖。机制上，发现 SNHG26 与核仁素（NCL）相互作用，从而通过增加其翻译来调节 c-Myc 的表达，进而通过己糖激酶 2（HK2）促进能量代谢，这有利于 GC 的恶性发展。增加的能量代谢为促进 c-Myc 翻译和表达提供了足够的能量，形成了正反馈回路。此外，代谢和翻译抑制剂可以阻断这个回路，从而抑制细胞增殖和迁移，这表明在 GC 中有潜在的治疗前景。
