研究动态
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通过以KSRP为依赖的方式,调控miR-320a生物生成,间基因环状RNA Circ_0007379抑制结直肠癌的进展。

Intergenic CircRNA Circ_0007379 Inhibits Colorectal Cancer Progression by Modulating miR-320a Biogenesis in a KSRP-Dependent Manner.

发表日期:2023
作者: Fei Long, Liang Li, Canbin Xie, Min Ma, Zhiwei Wu, Zhixing Lu, Baiying Liu, Ming Yang, Fan Zhang, Zhengping Ning, Chonglei Zhong, Bowen Yu, Shiyi Liu, Longyu Wan, Buning Tian, Kaiyan Yang, Yihang Guo, Miao Chen, Jin Chou, Xiaorong Li, Gui Hu, Changwei Lin, Yi Zhang
来源: International Journal of Biological Sciences

摘要:

环状RNA(circRNA)是共价封闭的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circRNA相比,人类癌症中的插入circRNA的生物学功能和意义仍知之甚少。在本研究中,我们进行了circRNA微阵列分析,并发现一个插入circRNA,circ_0007379,在结直肠癌(CRC)患者中显著下调。circ_0007379的生成是通过反向互补匹配(RCMs)介导的,并且受到RNA解旋酶DHX9的负调控。在功能上,circ_0007379在细胞培养以及患者来源的器官样和异种移植模型中抑制了CRC细胞的生长和转移。在机制上,circ_0007379作为一个平台,在KSRP依赖的情况下促进了pri-miR-320a和pre-miR-320a的加工,导致miR-320a成熟并抑制转录因子RUNX1的表达。因此,我们的发现在抑制CRC进展方面建立了一个以前未被认识的circRNA功能。©作者
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, circ_0007379, that was significantly downregulated in patients with colorectal cancer (CRC). The biogenesis of circ_0007379 was mediated by reverse complementary matches (RCMs) and was negatively regulated by the RNA helicase DHX9. Functionally, circ_0007379 suppressed CRC cell growth and metastasis in cell culture as well as in patient-derived organoid and xenograft models. Mechanistically, circ_0007379 acted as a scaffold to facilitate the processing of both pri-miR-320a and pre-miR-320a in a KSRP-dependent manner, leading to miR-320a maturation and subsequent repression of transcription factor RUNX1 expression. Thus, our findings establish a previously unrecognized function of circRNA in inhibiting CRC progression.© The author(s).