Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Oncol Rep. 2018 Jul;40(1):554-564. doi: 10.3892/or.2018.6449. Epub 2018 May 17.
Colorectal cancer (CRC) is reported to be the third most common cancer and the fourth leading cause of cancer-related deaths around the world. MicroRNA-485 (miR-485) has been reported to be aberrantly expressed and play important roles in several types of human malignancy. However, the expression level, biological functions and underlying molecular mechanisms of miR-485 in CRC remain unclear. Therefore, the aim of the present study was to determine miR-485 expression levels and their clinical significance in CRC and to explore the functions and underlying mechanisms of miR-485 in this disease. In the present study, miR-485 was lowly expressed in CRC tissues and cell lines. Decreased miR-485 expression was associated with tumour size, lymph node metastasis, distant metastasis and TNM stage. Functional assays indicated that upregulation of miR-485 impaired CRC cell proliferation, invasion and induced cell apoptosis. Grb2-associated binding 2 (GAB2) was identified as a direct target of miR-485 in CRC. GAB2 was upregulated in CRC tissues and was negatively correlated with the miR-485 expression level. Furthermore, GAB2 knockdown simulated the tumour-suppressing roles of miR-485 overexpression in CRC cells. Moreover, restored GAB2 expression reversed the effects of miR-485 overexpression in CRC cells. In addition, miR-485 suppressed the AKT and ERK signalling pathways in CRC by directly targeting GAB2. Collectively, these findings demonstrate that miR-485 may play tumour suppressive roles in CRC by directly targeting GAB2 and indirectly regulating AKT and ERK signalling pathways, suggesting that miR-485 may be a potential therapeutic target for patients with this disease.
结直肠癌(CRC)据报道是全球第三大常见癌症和第四大癌症相关死亡原因。microRNA-485(miR-485)已被报道存在异常表达,并在多种人类恶性肿瘤中发挥重要作用。然而,miR-485 在 CRC 中的表达水平、生物学功能和潜在分子机制仍不清楚。因此,本研究旨在确定 miR-485 在 CRC 中的表达水平及其临床意义,并探讨 miR-485 在该疾病中的功能和潜在机制。在本研究中,miR-485 在 CRC 组织和细胞系中低表达。miR-485 表达降低与肿瘤大小、淋巴结转移、远处转移和 TNM 分期有关。功能测定表明,上调 miR-485 可损害 CRC 细胞增殖、侵袭并诱导细胞凋亡。Grb2 相关结合蛋白 2(GAB2)被鉴定为 CRC 中 miR-485 的直接靶标。GAB2 在 CRC 组织中上调,与 miR-485 的表达水平呈负相关。此外,GAB2 敲低模拟了 miR-485 过表达在 CRC 细胞中的肿瘤抑制作用。此外,恢复 GAB2 表达逆转了 miR-485 过表达对 CRC 细胞的作用。此外,miR-485 通过直接靶向 GAB2 抑制 CRC 中的 AKT 和 ERK 信号通路。总之,这些发现表明,miR-485 通过直接靶向 GAB2 并间接调节 AKT 和 ERK 信号通路,在 CRC 中可能发挥肿瘤抑制作用,表明 miR-485 可能是该疾病患者的潜在治疗靶点。