Department of General Surgery, Affiliated Hospital of Chifeng University, No. 42 Wangfu Street, Songshan, Chifeng, 024005, China.
Cell Mol Biol Lett. 2022 Mar 2;27(1):22. doi: 10.1186/s11658-022-00322-y.
miR-152-3p functions as a tumour suppressor in the progression of hepatic tumorigenesis. Herein, we further discussed the prognostic significance and immune infiltration of miR-152-3p and its potential gene target in hepatocellular carcinoma (HCC).
The Cancer Genome Atlas (TCGA), Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), Human Protein Atlas (HPA) and Kaplan-Meier Plotter databases were used to evaluate miR-152-3p and roundabout guidance receptor 1 (ROBO1) expression, prognosis and immune infiltration. In vitro cell experiments, including cell proliferation and apoptosis, were evaluated using Cell Counting Kit 8 (CCK8) and terminal-deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) assays.
Up-regulation of ROBO1 functioned as an oncogene associated with poor prognosis, immune cell enrichment and cell proliferation in HCC. ROBO1 was significantly positively correlated with the enrichment of multiple immune cells and their biomarkers. Enrichment of type-2 T-helper (Th2) cells is an unfavourable biomarker of HCC prognosis. GSEA revealed that ROBO1 correlated with apoptosis, mitosis and carcinogenic signalling pathways. Suppression of cell proliferation and the enhancement of cell apoptosis by miR-152-3p mimics were counteracted by overexpression of ROBO1 in HCC cells.
ROBO1 expression is positively correlated with multiple immune checkpoint molecules, suggesting that ROBO1 may be a potential drug target to enhance the potency of immunotherapy. The miR-152-3p/ROBO1 signalling axis contributes to malignant progression and provides a prospective immunotherapeutic target for HCC.
miR-152-3p 在肝肿瘤发生进展中作为一种肿瘤抑制因子发挥作用。在此，我们进一步探讨了 miR-152-3p 在肝细胞癌（HCC）中的预后意义和免疫浸润及其潜在的基因靶标。
使用癌症基因组图谱（TCGA）、肝细胞癌综合分子数据库（HCCDB）、人类蛋白质图谱（HPA）和 Kaplan-Meier Plotter 数据库评估 miR-152-3p 和绕路引导受体 1（ROBO1）的表达、预后和免疫浸润。体外细胞实验，包括细胞增殖和凋亡，通过 Cell Counting Kit 8（CCK8）和末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）实验进行评估。
ROBO1 功能上调是与 HCC 预后不良、免疫细胞富集和细胞增殖相关的癌基因。ROBO1 与多种免疫细胞及其标志物的富集呈显著正相关。2 型辅助性 T 细胞（Th2）细胞的富集是 HCC 预后不良的生物标志物。GSEA 表明，ROBO1 与细胞凋亡、有丝分裂和致癌信号通路相关。miR-152-3p 模拟物对 HCC 细胞增殖的抑制和细胞凋亡的增强作用被 ROBO1 的过表达所拮抗。
ROBO1 的表达与多种免疫检查点分子呈正相关，表明 ROBO1 可能是增强免疫疗法效力的潜在药物靶点。miR-152-3p/ROBO1 信号轴促进恶性进展，为 HCC 提供了一个有前景的免疫治疗靶点。
