Lu Yan, Liu Yao, Zhang Ke, Jiang Li
Department of Hepatobiliary Surgery, Beijing Ditan Hospital Capital Medical University, 100015 Beijing, China.
Department of Surgery, Fuwai Hospital, Chinese Academy of Medical Science, 100037 Beijing, China.
J Oncol. 2022 Mar 22;2022:2415836. doi: 10.1155/2022/2415836. eCollection 2022.
Mounting evidence has shown that circular RNAs (circRNAs) function as key regulators in carcinogenesis and cancer progression, and this study is aimed at investigating the regulatory functions of circRNA TLK1 (circ-TLK1) in hepatocellular carcinoma (HCC). We observed that circ-TLK1 was highly expressed in HCC samples, and its high expression was closely associated with poor clinicopathological variables of HCC patients. The results of functional experiments revealed that knockdown of circ-TLK1 remarkably inhibited the proliferation, migration, invasion, and EMT of HCC cells, while circ-TLK1 overexpression promoted these malignant behaviors. Moreover, we noted that circ-TLK1 was capable of binding to miR-138-5p and upregulating its target gene, SOX4 in HCC. Based on rescue assays, miR-138-5p inhibition partially suppressed the effects of circ-TLK1 knockdown on the malignant behaviors of HCC cells. In short, this study is the first to indicate that circ-TLK1 functions as an oncogene in HCC progression partly through acting as a ceRNA of miR-138-5p, which may be a promising target for HCC therapy.
越来越多的证据表明，环状RNA（circRNA）在肿瘤发生和癌症进展中起关键调节作用，本研究旨在探讨环状RNA TLK1（circ-TLK1）在肝细胞癌（HCC）中的调节功能。我们观察到circ-TLK1在HCC样本中高表达，其高表达与HCC患者不良的临床病理特征密切相关。功能实验结果显示，敲低circ-TLK1可显著抑制HCC细胞的增殖、迁移、侵袭和上皮-间质转化（EMT），而circ-TLK1过表达则促进这些恶性行为。此外，我们注意到circ-TLK1能够与miR-138-5p结合并上调其在HCC中的靶基因SOX4。基于挽救实验，抑制miR-138-5p可部分抑制circ-TLK1敲低对HCC细胞恶性行为的影响。简而言之，本研究首次表明circ-TLK1在HCC进展中作为癌基因发挥作用，部分是通过充当miR-138-5p的竞争性内源RNA（ceRNA），这可能是HCC治疗的一个有前景的靶点。
