1 Department of Organ Transplantation, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Cancer Control. 2019 Jan-Dec;26(1):1073274819846593. doi: 10.1177/1073274819846593.
MicroRNAs (miRNAs), a subgroup of small noncoding RNAs, play critical roles in tumor growth and metastasis. Accumulating evidence shows that the dysregulation of miRNAs is associated with the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism by which miR-942-3p contributes to HCC remains undocumented. The association between miR-942-3p expression and the clinicopathological characteristics in HCC patients was analyzed by The Cancer Genome Atlas data set. The targets of miR-942-3p were identified by bioinformatic analysis and dual luciferase report assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays were performed to assess the functional role of miR-942-3p in HCC cells. Consequently, we found that miR-942-3p expression level was elevated in HCC tissues and cell lines as compared with the normal tissues and was associated with the pathological stage and tumor node metastasis (TNM) stage, acting as an independent prognostic factor of poor survival in patients with HCC. Ectopic expression of miR-942-3p enhanced the proliferation and invasive potential of HCC cells, but inhibition of miR-942-3p expression had the opposite effects. Mannose-binding lectin 2 (MBL2) was further identified as a direct target of miR-942-3p and possessed a negative correlation with miR-942-3p expression and unfavorable survival in patients with HCC. Restoration of MBL2 inhibited the progression of HCC cells and attenuated the tumor-promoting effects induced by miR-942-3p. In conclusion, miR-942-3p may act as an oncogenic factor in HCC cells by targeting MBL2 and provide a potential marker for patients with HCC.
微小 RNA(miRNAs)是一类小型非编码 RNA,在肿瘤生长和转移中发挥着关键作用。越来越多的证据表明,miRNAs 的失调与肝细胞癌(HCC)的进展有关。然而,miR-942-3p 促进 HCC 的分子机制仍未被记录。通过癌症基因组图谱数据集分析 miR-942-3p 表达与 HCC 患者临床病理特征之间的关系。通过生物信息学分析和双荧光素酶报告实验鉴定 miR-942-3p 的靶标。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)和 Transwell 实验用于评估 miR-942-3p 在 HCC 细胞中的功能作用。结果发现,与正常组织相比,HCC 组织和细胞系中 miR-942-3p 的表达水平升高,并且与病理分期和肿瘤淋巴结转移(TNM)分期相关,是 HCC 患者不良生存的独立预后因素。miR-942-3p 的异位表达增强了 HCC 细胞的增殖和侵袭能力,但抑制 miR-942-3p 的表达则产生相反的效果。甘露糖结合凝集素 2(MBL2)进一步被鉴定为 miR-942-3p 的直接靶标,与 miR-942-3p 的表达呈负相关,并且与 HCC 患者的不良生存相关。MBL2 的恢复抑制了 HCC 细胞的进展,并减弱了 miR-942-3p 诱导的促肿瘤作用。总之,miR-942-3p 可能通过靶向 MBL2 作为 HCC 细胞中的致癌因子,并为 HCC 患者提供潜在的标志物。