Wang Shuo, Wang Tianjiao, Gu Pengcheng
Department of Orthopedics Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, People's Republic of China.
Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People's Republic of China.
Cancer Manag Res. 2021 Apr 21;13:3473-3484. doi: 10.2147/CMAR.S300678. eCollection 2021.
Hepatocellular carcinoma (HCC) has the fourth highest rate of mortality among the different types of cancer worldwide. This study aimed to investigate the functions of microRNA-145-5p and AFR6 on migration, invasion and metastasis in HCC.
A total of 150 pairs of tumor and their matched adjacent nontumor liver tissues were collected from HCC patients. Expressions of microRNA-145-5p and AFR6 were measured by real-time PCR in HCC tissues and in HCC cell lines. The correlations between microRNA-145-5p and HCC prognosis were investigated. The proliferation, migration, invasion, cell cycle progression, and apoptosis of HCCLM3 cells were evaluated with CCK8, wound healing, transwell, and flow cytometric experiments.
The expression of miR-145-5p was confirmed to be downregulated not only in HCC tissues but also in several HCC cell lines compared with normal controls. A low expression level of miR-145-5p was notably associated with poor prognosis in patients with HCC and certain characteristics of metastatic tumors. In vitro, miR-145-5p negatively regulated cell proliferation, migration, and invasion and induced apoptosis in HCCLM3 cells. Subsequent experiments further verified that ARF6 is a novel target of miR-145-5p and is significantly overexpressed in HCC tissues. Overexpression of ARF6 circumvented the effects of miR-145-5p in HCCLM3 cells.
miR-145-5p may play a pivotal role in HCC metastasis via regulating ARF6, and these findings may both provide further insights into the key factors of HCC metastasis and prove to be useful in the development of novel treatment options for HCC.
在全球不同类型癌症中，肝细胞癌（HCC）的死亡率位居第四。本研究旨在探讨微小RNA - 145 - 5p和AFR6在HCC迁移、侵袭和转移中的作用。
从HCC患者中收集了150对肿瘤及其匹配的相邻非肿瘤肝组织。通过实时PCR检测HCC组织和HCC细胞系中微小RNA - 145 - 5p和AFR6的表达。研究微小RNA - 145 - 5p与HCC预后的相关性。用CCK8、伤口愈合、transwell和流式细胞术实验评估HCCLM3细胞的增殖、迁移、侵袭、细胞周期进程和凋亡。
与正常对照相比，miR - 145 - 5p的表达不仅在HCC组织中下调，在几种HCC细胞系中也下调。miR - 145 - 5p低表达水平与HCC患者的不良预后及转移瘤的某些特征显著相关。在体外，miR - 145 - 5p负向调节HCCLM3细胞的增殖、迁移和侵袭并诱导其凋亡。后续实验进一步证实ARF6是miR - 145 - 5p的一个新靶点，且在HCC组织中显著过表达。ARF6的过表达抵消了miR - 145 - 5p对HCCLM3细胞的影响。
miR - 145 - 5p可能通过调节ARF6在HCC转移中起关键作用，这些发现可能为HCC转移的关键因素提供进一步见解，并证明对开发HCC的新治疗方案有用。
