circSORBS1 inhibits lung cancer progression by sponging miR-6779-5p and directly binding RUFY3 mRNA

circSORBS1 通过吸收 miR-6779-5p 并直接结合 RUFY3 mRNA 来抑制肺癌进展

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作者:Haotian Xu #, Yue Zheng #, Jiaxi Wu #, Ruirui Zhang, Qingyun Zhao, Sixian Chen, Wenyi Peng, Dunyu Cai, Yihong Gao, Xingcai Chen, Deqing Li, Shengyi Yuan, Gang Li, Aruo Nan

Abstract

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.

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