Wang Xiaodong, Lu Jian, Cao Jisen, Ma Bozhao, Gao Chao, Qi Feng
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China,
Department of Hepatobiliary Surgery, Tianjin Third Center Hospital, Tianjin, China.
Onco Targets Ther. 2018 Nov 9;11:7919-7934. doi: 10.2147/OTT.S180971. eCollection 2018.
Hepatocellular carcinoma (HCC) is known to feature several microRNA dysregulations. This study aimed to determine and investigate the prognostic value of microRNA (miRNA/miR)-18a and its role in regulating the progression of HCC.
miR-18a expressions in human HCC tissues, pair-matched adjacent normal liver tissues as well as in HCC cell lines were determined by quantitative real-time PCR. The prognostic value of miR-18a was determined using Kaplan-Meier survival analysis and multivariable Cox regression assay. The ability of miR-18a in promoting HCC progression was verified in vitro.
miR-18a expressions in HCC tissues and cells were more than twice those of the normal control group (<0.05). miR-18a expression was associated with the alpha-fetoprotein (AFP) level, TNM stage, tumor size, and intrahepatic vascular invasion (<0.05). Kaplan- Meier survival analysis revealed that HCC patients with high expression of miR-18a possessed a more unfavorable prognosis (log-rank <0.001). Overexpression of miR-18a promoted cell apoptosis and proliferation, induced S phase transition, as well as enhanced the migration and invasion ability of HCC cells. miR-18a was found to directly target the downstream molecule Bcl2L10. Furthermore, overexpressing Bcl2L10 was able to partly reverse the promoting effects of miR-18a on HCC cell progression.
miR-18a may serve as a prognostic biomarker of HCC as it is demonstrated to carry out a decisive role in HCC progression by promoting HCC cell invasion, migration, and proliferation through targeting Bcl2L10.
已知肝细胞癌(HCC)存在多种微小RNA失调。本研究旨在确定并调查微小RNA(miRNA/miR)-18a的预后价值及其在调节HCC进展中的作用。
采用定量实时PCR法检测人HCC组织、配对的相邻正常肝组织以及HCC细胞系中miR-18a的表达。使用Kaplan-Meier生存分析和多变量Cox回归分析确定miR-18a的预后价值。在体外验证miR-18a促进HCC进展的能力。
HCC组织和细胞中miR-18a的表达是正常对照组的两倍多(<0.05)。miR-18a表达与甲胎蛋白(AFP)水平、TNM分期、肿瘤大小及肝内血管侵犯相关(<0.05)。Kaplan-Meier生存分析显示,miR-18a高表达的HCC患者预后更差(对数秩<0.001)。miR-18a过表达促进细胞凋亡和增殖,诱导S期转变,并增强HCC细胞的迁移和侵袭能力。发现miR-18a直接靶向下游分子Bcl2L10。此外,过表达Bcl2L10能够部分逆转miR-18a对HCC细胞进展的促进作用。
miR-18a可能作为HCC的预后生物标志物,因为它通过靶向Bcl2L10促进HCC细胞侵袭、迁移和增殖,在HCC进展中起决定性作用。