He Chunping, Huang Chao, Zhou Rui, Yu Honggang
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China.
Onco Targets Ther. 2019 Aug 9;12:6349-6359. doi: 10.2147/OTT.S204741. eCollection 2019.
The aberrant expression of circular RNAs (circRNAs) is a frequent occurrence in various cancers. However, the functions and roles played by most circRNAs in colorectal cancer (CRC) remain largely unknown.
Levels of circLMNB1 expression were evaluated by qRT-PCR and FISH assays. The influence of circLMNB1 knockdown on LoVo and HCT116 cell proliferation, cycling, apoptosis, migration, and invasion were assessed by the CCK-8, assay, Edu assay, flow cytometry, Hoechst staining, and the Transwell assay, respectively. The relative levels of EMT- and apoptosis-related proteins were determined by Western blotting.
CircLMNB1 expression was significantly upregulated in CRC tissues and cells. Knockdown of circLMNB1 by siRNA in LoVo cells suppressed cell proliferation, migration and invasion, and facilitated cell cycle arrest and apoptosis In addition, we proved that knockdown of circLMNB1 upregulated E-cadherin, Bax and caspase-3 expression, and downregulated MMP2, MMP-9, and N-cadherin expression in LoVo cells. Further results showed that overexpression of circLMNB1 enhanced the malignant characteristics of HCT116 cells.
Our findings revealed that blocking of circLMNB1 could inhibit CRC development, and help to explain the underlying mechanism by which circLMNB1 knockdown inhibits the metastasis of CRC. Finally, this study suggests circLMNB1 as a novel biomarker for CRC.
环状RNA（circRNA）的异常表达在多种癌症中频繁出现。然而，大多数circRNA在结直肠癌（CRC）中的功能和作用仍 largely未知。
通过qRT-PCR和FISH检测评估circLMNB1的表达水平。分别通过CCK-8检测、Edu检测、流式细胞术、Hoechst染色和Transwell检测评估circLMNB1敲低对LoVo和HCT116细胞增殖、周期、凋亡、迁移和侵袭的影响。通过蛋白质印迹法测定EMT和凋亡相关蛋白的相对水平。
circLMNB1在CRC组织和细胞中显著上调。在LoVo细胞中通过siRNA敲低circLMNB1可抑制细胞增殖、迁移和侵袭，并促进细胞周期停滞和凋亡。此外，我们证明敲低circLMNB1可上调LoVo细胞中E-钙黏蛋白、Bax和caspase-3的表达，并下调MMP2、MMP-9和N-钙黏蛋白的表达。进一步结果表明，circLMNB1的过表达增强了HCT116细胞的恶性特征。
我们的研究结果表明，阻断circLMNB1可抑制CRC的发展，并有助于解释circLMNB1敲低抑制CRC转移的潜在机制。最后这项研究表明circLMNB1是一种新的CRC生物标志物。
