School of Public Health, Guangxi Medical University, Nanning, 530021, China.
Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning, 530021, China.
J Transl Med. 2024 Jun 24;22(1):590. doi: 10.1186/s12967-024-05423-0.
Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.
肺癌是全球癌症相关死亡的主要原因，其全球发病率和死亡率仍然很高。环状 RNA（circRNA）的差异表达可以影响癌症的发展，但 circRNA 调节肺癌进展的机制尚不清楚。在本研究中，我们鉴定了 circSORBS1，这是一种以前在肺癌中未被描述的 circRNA，在肺癌组织、血液和细胞系中表达显著下调，circSORBS1 的低表达与肿瘤分级和预后相关。体外和体内功能实验表明，circSORBS1 的过表达抑制细胞增殖和迁移，同时促进细胞凋亡。机制上，circSORBS1 作为 miR-6779-5p 的海绵，间接抑制 RUFY3 mRNA 的降解。同时，它与 RUFY3 mRNA 结合以增强其稳定性。这种双重调节机制导致 RUFY3 蛋白水平的增加，最终激活 YWHAE/BAD/BCL2 凋亡信号通路并抑制肺癌的进展。我们的研究结果不仅增加了对 circRNA 表达调控模式的认识，而且为 circRNA 调节肺癌发生发展的机制提供了新的见解。
