Departments of General Surgery, General Hospital of Lanzhou Petrochemical Company, Lanzhou 730060, Gansu, China.
Department of Pharmacy, General Hospital of Lanzhou Petrochemical Company, Lanzhou 730060, Gansu, China.
Gene. 2019 May 25;698:141-149. doi: 10.1016/j.gene.2019.02.071. Epub 2019 Mar 5.
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, with characteristics of high morbidity and mortality. Identifying clinically practical targets and uncovering the potential mechanism for HCC were urgent for us. Though aberrantly expressed miR-99b-3p has been reported in several cancers, the expression and roles of miR-99b-3p in HCC remain uncovered. In the present study, we demonstrated for the first time that miR-99b-3p was overexpressed in HCC by our findings and data from GEO datasets. Statistical analysis revealed that highly expressed miR-99b-3p was closely related to malignant clinicopathological characteristics and poorer prognosis of HCC patients. Furthermore, results from Wound healing assay, Transwell assays, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay and 5-ethynyl-2'-deoxyuridine (EdU) assay revealed that miR-99b-3p played a promoting role in migration, invasion and proliferation of HCC cells. Then, by bioinformatics tools, luciferase reporter gene assay, integrative database analysis, and Pearson correlation analysis and so on, protocadherin 19 (PCDH19) was identified as the target of miR-99b-3p in HCC cells. Furthermore, rescue experiments were conducted to confirm the mediator role of PCDH19 for miR-99b-3p. Collectively, we demonstrate that miR-99b-3p promotes HCC metastasis and proliferation by directly targeting PCDH19. MiR-99b-3p may become a potential therapy target for HCC.
肝细胞癌 (HCC) 是世界上最常见的癌症之一,具有高发病率和死亡率的特点。确定临床上实用的靶点并揭示 HCC 的潜在机制对我们来说迫在眉睫。尽管异常表达的 miR-99b-3p 已在几种癌症中报道,但 miR-99b-3p 在 HCC 中的表达和作用仍未被揭示。在本研究中,我们首次通过我们的发现和 GEO 数据集的数据表明,miR-99b-3p 在 HCC 中过表达。统计分析显示,高表达的 miR-99b-3p 与 HCC 患者恶性临床病理特征和较差的预后密切相关。此外,划痕愈合试验、Transwell 试验、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐 (MTT) 试验和 5-乙炔基-2'-脱氧尿苷 (EdU) 试验的结果表明,miR-99b-3p 促进了 HCC 细胞的迁移、侵袭和增殖。然后,通过生物信息学工具、荧光素酶报告基因检测、综合数据库分析和 Pearson 相关性分析等,确定原钙黏蛋白 19 (PCDH19) 是 HCC 细胞中 miR-99b-3p 的靶基因。此外,还进行了挽救实验以确认 PCDH19 是 miR-99b-3p 的介体作用。综上所述,我们证明 miR-99b-3p 通过直接靶向 PCDH19 促进 HCC 的转移和增殖。miR-99b-3p 可能成为 HCC 的潜在治疗靶点。