Hao Shunxin, Yao Zhi, Liu Yifeng
Department of General Surgery, Wuhan University of Science and Technology Hospital, Wuhan, China.
Horm Metab Res. 2023 Oct;55(10):722-732. doi: 10.1055/a-2125-7018. Epub 2023 Aug 8.
Circular RNAs (circRNAs) frequently participate in pancreatic cancer (PC) progression. This study focuses on circ_0000106, a novel circRNA, and its potential function in PC development. Circ_00001106, miR-455-3p, and HDAC4 expression levels in PC were determined using qRT-PCR and immunoblotting. RNA immunoprecipitation and dual-luciferase reporter assays were performed to verify their binding interactions. Loss-of-function assays, including CCK-8, colony formation, and transwell assays, were used to estimate the proliferative and migratory properties of PC cells. A nude mouse model was constructed to assess the influence of circ_0000106 on tumor formation in vivo. A pronounced elevation of circ_0000106 and HDAC4 and a reduction of miR-455-3p in PC were observed. Circ_0000106 was prone to binding to miR-455-3p, and miR-455-3p further targeted HDAC4. Functionally, the proliferative and migratory properties of PC cells were dampened by the loss of circ_0000106 or HDAC4 and could be potentiated by miR-455-3p inhibition. Moreover, the knockdown of circ_0000106 delayed tumor growth in vivo. Additionally, the downregulation of miR-455-3p attenuated the repressive effects of circ_0000106 deficiency on PC cell migration and proliferation. Loss of HDAC4 exerted similar mitigative effects on miR-455-3p downregulation-stimulated PC cells. In conclusion, circ_0000106 promotes tumor migration and growth in PC by targeting the miR-455-3p/HDAC4 axis. These results suggest that the circ_0000106/miR-455-3p/HDAC4 network could be regarded as a latent target for PC treatment.
环状RNA（circRNAs）频繁参与胰腺癌（PC）的进展。本研究聚焦于一种新型环状RNA——circ_0000106及其在PC发生发展中的潜在功能。采用qRT-PCR和免疫印迹法测定PC中circ_00001106、miR-455-3p和HDAC4的表达水平。进行RNA免疫沉淀和双荧光素酶报告基因检测以验证它们之间的结合相互作用。采用包括CCK-8、集落形成和Transwell检测在内的功能缺失实验来评估PC细胞的增殖和迁移特性。构建裸鼠模型以评估circ_0000106对体内肿瘤形成的影响。观察到PC中circ_0000106和HDAC4明显升高，而miR-455-3p降低。circ_0000106易于与miR-455-3p结合，且miR-455-3p进一步靶向HDAC4。在功能上，circ_0000106或HDAC4的缺失会抑制PC细胞的增殖和迁移特性，而miR-455-3p抑制则可增强这些特性。此外，circ_0000106的敲低会延迟体内肿瘤生长。此外，miR-455-3p的下调减弱了circ_0000106缺失对PC细胞迁移和增殖的抑制作用。HDAC4的缺失对miR-455-3p下调刺激的PC细胞产生类似的缓解作用。总之，circ_0000106通过靶向miR-455-3p/HDAC4轴促进PC中的肿瘤迁移和生长。这些结果表明，circ_0000106/miR-455-3p/HDAC4网络可被视为PC治疗的潜在靶点。
