Xu Rui, He Haitao, Wang Yue, Peng Qi, Mei Ke, Liu Yan, Yang Qing
Jilin University, College of Basic Medical Sciences, Department of Pathogenobiology, Changchun, Jilin Province, China.
Jilin University, College of Basic Medical Sciences, Department of Cell Biology, Changchun, Jilin Province, China.
Genet Mol Biol. 2023 Jun 2;46(2):e20220277. doi: 10.1590/1678-4685-GMB-2022-0277. eCollection 2023.
Long non-coding RNA AK001796 was initially identified altered in lung cancer. Recent research showed it could participate in the prognosis of hepatocellular carcinoma (HCC). However, the general biological role of AK001796 and its underlying mechanisms in HCC remain unclear. Here we demonstrated that the expression level of AK001796 in HCC tissues and cell lines was up-regulated. Silencing AK001796 suppressed the proliferation ability of HCC cells. Through dual luciferase reporter assays and loss/gain of functions studies, we identified that AK001796 could bind to miR-150, a star microRNA, promoting HCC proliferation. Furthermore, it was reported that growth factor receptor binding protein 2-associated binder 1 (GAB1) is a target gene of miR-150. Owing to AK001796 being a decoy for miR-150 and binding the same putative sites of miR-150 as GAB1, we presented that inhibition of miR-150 in AK001796 silencing cells reversed the reduction in GAB1. Subsequently, our findings demonstrated that silencing AK001796 can impair phospho-ERK1/2 and phospho-AKT. In conclusion, our investigation revealed that AK001796 promoted proliferation by enhancing phospho-ERK1/2 and phospho-AKT through AK001796/miR-150/GAB1 axis in HCC. These results provided further evidence for the critical roles of AK001796 accumulating HCC and suggested that AK001796 might act as an HCC biomarker in clinical treatment.
长链非编码RNA AK001796最初被鉴定为在肺癌中发生改变。最近的研究表明它可能参与肝细胞癌(HCC)的预后。然而,AK001796在HCC中的一般生物学作用及其潜在机制仍不清楚。在此我们证明,AK001796在HCC组织和细胞系中的表达水平上调。沉默AK001796可抑制HCC细胞的增殖能力。通过双荧光素酶报告基因分析和功能缺失/获得研究,我们确定AK001796可以与一种明星微小RNA miR-150结合,促进HCC增殖。此外,据报道生长因子受体结合蛋白2相关结合蛋白1(GAB1)是miR-150的靶基因。由于AK001796是miR-150的诱饵,并与GAB1结合miR-150的相同假定位点,我们提出在AK001796沉默细胞中抑制miR-150可逆转GAB1的减少。随后,我们的研究结果表明沉默AK001796会损害磷酸化ERK1/2和磷酸化AKT。总之,我们的研究揭示了AK001796通过AK001796/miR-150/GAB1轴增强磷酸化ERK1/2和磷酸化AKT来促进HCC增殖。这些结果为AK001796在HCC积累中的关键作用提供了进一步的证据,并表明AK001796可能在临床治疗中作为HCC的生物标志物。