Fei Zhenghua, Wang Yanfen, Gu Yuyang, Xie Rongrong, Hao Qiongyu, Jiang Yiyan
Department of Radiotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Pathology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China.
Front Oncol. 2022 Jun 30;12:916246. doi: 10.3389/fonc.2022.916246. eCollection 2022.
The long-term prognosis of HCC (hepatocellular carcinoma) with metastasis remains extremely poor. CircRNAs are promising as critical biological markers in identifying disease mechanisms and developing new effective treatments. However, the role of the aberrant expression of circRNAs in HCC progression remains largely unknown.
CircKIF5B location was investigated by RNA fluorescence hybridization (RNA-FISH). For circRNA determination, RNase R treatment and Real-Time Quantitative RT-PCR (qRT-PCR) were performed. Transwell chamber assays examined the chemotactic migration and invasion of liver cancer cells.
This study identified the circRNA circKIF5B originating from exons 1, 2, and 3 of the KIF5B gene. Importantly, we found that circKIF5B circRNA, rather than KIF5B linear mRNA, was notably upregulated in liver cancer cell lines and tissues. Moreover, we found that silencing circKIF5B markedly reduced the proliferation, invasion, and metastasis of liver cancer cells by sponging the miR-192 family, thus decreasing the expression of X-linked inhibitor of apoptosis (XIAP).
Our data demonstrate that circKIF5B can regulate XIAP expression by sponging miR-192 and miR-215 competing for the ceRNA mechanism, indicating that circKIF5B may act as an essential upstream regulator and providing mechanistic evidence to support the view that circKIF5B/miR-192s/XIAP is a promising therapeutic target for treating liver cancer.
发生转移的肝细胞癌（HCC）的长期预后仍然极差。环状RNA（circRNAs）有望成为识别疾病机制和开发新的有效治疗方法的关键生物标志物。然而，circRNAs异常表达在HCC进展中的作用仍 largely未知。
通过RNA荧光杂交（RNA-FISH）研究环状KIF5B的定位。对于环状RNA的测定，进行了核糖核酸酶R处理和实时定量逆转录聚合酶链反应（qRT-PCR）。Transwell小室试验检测了肝癌细胞的趋化迁移和侵袭。
本研究鉴定了源自KIF5B基因外显子1、2和3的环状RNA circKIF5B。重要的是，我们发现环状KIF5B circRNA而非KIF5B线性mRNA在肝癌细胞系和组织中显著上调。此外，我们发现沉默circKIF5B通过海绵化miR-192家族显著降低了肝癌细胞的增殖、侵袭和转移，从而降低了X连锁凋亡抑制蛋白（XIAP）的表达。
我们的数据表明，circKIF5B可通过海绵化miR-192和miR-215竞争ceRNA机制来调节XIAP表达，表明circKIF5B可能作为一个重要的上游调节因子，并提供机制证据支持circKIF5B/miR-192s/XIAP是治疗肝癌的一个有前景的治疗靶点这一观点。
