Li Zhiqin, Hu Yushu, Zeng Qinglei, Wang Hongyan, Yan Jingya, Li Hua, Yu Zujiang
Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou, 450052 Henan People's Republic of China.
Cancer Cell Int. 2019 Aug 8;19:211. doi: 10.1186/s12935-019-0926-7. eCollection 2019.
CircRNA myosin light chain kinase (circRNA MYLK) has been shown to promote the progression of various tumor diseases. The purpose of this study was to explore the potential molecular mechanism of circMYLK in hepatocellular carcinoma (HCC).
The quantitative Real-Time PCR (qRT-PCR) was used to measure the expressions of circMYLK, miR-362-3p and Rab23 in HCC tissues and cell lines. Huh7 and Hep3B cells were selected to explore the role of circMYLK in proliferation, invasion and migration of HCC cells in vitro. The interaction among circMYLK, miR-362-3p and Rab23 was investigated by biological information and dual luciferase gene reporter assay. The effect of circMYLK on HCC tumor growth in vivo was studied in a tumor xenograft model in mice.
CircMYLK was highly expressed in HCC tissues and cell lines, which was associated with poor prognosis in HCC patients. In addition, knockdown of circMYLK remarkably inhibited the proliferation, invasion, and migration of Huh7 and Hep3B cells. MiR-362-3p was a direct target of circMYLK, and Rab23 was a direct target gene of miR-362-3p. Meanwhile, circMYLK was negatively correlated with the expression of miR-362-3p and positively correlated with Rab23 expression. Moreover, either overexpressed miR-362-3p or silencing Rab23 could observably suppress the enhanced proliferation, invasion, and migration induced by circMYLK in Huh7 and Hep3B cells. Finally, knockdown of circMYLK and overexpressed miR-362-3p could suppress the expression of Rab23, thus inhibiting the growth and proliferation of Hep3B cells in vivo.
circMYLK promotes the occurrence and development of HCC by regulating the miR-362-3p/Rab23 axis, which provides a novel direction and theoretical basis for the early diagnosis and treatment of HCC.
环状RNA肌球蛋白轻链激酶（circRNA MYLK）已被证明可促进多种肿瘤疾病的进展。本研究旨在探讨circMYLK在肝细胞癌（HCC）中的潜在分子机制。
采用定量实时荧光定量PCR（qRT-PCR）检测HCC组织和细胞系中circMYLK、miR-362-3p和Rab23的表达。选用Huh7和Hep3B细胞，探讨circMYLK在体外对HCC细胞增殖、侵袭和迁移的作用。通过生物信息学和双荧光素酶基因报告试验研究circMYLK、miR-362-3p和Rab23之间的相互作用。在小鼠肿瘤异种移植模型中研究circMYLK对HCC肿瘤体内生长的影响。
circMYLK在HCC组织和细胞系中高表达，这与HCC患者的不良预后相关。此外，敲低circMYLK显著抑制Huh7和Hep3B细胞的增殖、侵袭和迁移。miR-362-3p是circMYLK的直接靶点，Rab23是miR-362-3p的直接靶基因。同时，circMYLK与miR-362-3p的表达呈负相关，与Rab23的表达呈正相关。此外，过表达miR-362-3p或沉默Rab23均可显著抑制circMYLK诱导的Huh7和Hep3B细胞增殖、侵袭和迁移增强。最后，敲低circMYLK和过表达miR-362-3p可抑制Rab23的表达，从而抑制Hep3B细胞在体内的生长和增殖。
circMYLK通过调节miR-362-3p/Rab23轴促进HCC的发生发展，为HCC的早期诊断和治疗提供了新的方向和理论依据。
