Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Postdoctoral Research Station of Basic Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Int J Biol Sci. 2023 Jul 24;19(12):3781-3803. doi: 10.7150/ijbs.85063. eCollection 2023.
Circular RNAs (circRNAs) are covalently closed RNA structures that play multiple roles in tumorigenesis and progression. Compared with exon‒intron circRNAs, the biological functions and implications of intergenic circRNAs in human cancer are still poorly understood. Here, we performed circRNA microarray analysis and identified an intergenic circRNA, , that was significantly downregulated in patients with colorectal cancer (CRC). The biogenesis of was mediated by reverse complementary matches (RCMs) and was negatively regulated by the RNA helicase DHX9. Functionally, suppressed CRC cell growth and metastasis in cell culture as well as in patient-derived organoid and xenograft models. Mechanistically, acted as a scaffold to facilitate the processing of both and in a KSRP-dependent manner, leading to maturation and subsequent repression of transcription factor RUNX1 expression. Thus, our findings establish a previously unrecognized function of circRNA in inhibiting CRC progression.
环状 RNA（circRNAs）是共价闭合的 RNA 结构，在肿瘤发生和进展中发挥多种作用。与外显子-内含子 circRNAs 相比，基因间 circRNAs 在人类癌症中的生物学功能和意义仍知之甚少。在这里，我们进行了 circRNA 微阵列分析，鉴定出一种基因间 circRNA ，在结直肠癌（CRC）患者中显著下调。的生物发生是由反向互补匹配（RCMs）介导的，并受 RNA 解旋酶 DHX9 的负调控。功能上，在细胞培养以及患者来源的类器官和异种移植模型中抑制 CRC 细胞的生长和转移。在机制上，作为支架，以促进在 KSRP 依赖性方式处理和，导致成熟和随后抑制转录因子 RUNX1 的表达。因此，我们的研究结果确立了 circRNA 在抑制 CRC 进展中的一个以前未被认识的功能。
