Department of Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Mol Med Rep. 2017 Oct;16(4):4437-4444. doi: 10.3892/mmr.2017.7130. Epub 2017 Aug 1.
Plant homeo domain finger protein 8 (PHF8), as an oncogene, has been highlighted in cancer development and progression. However, its clinical significance and underlying molecular mechanisms in colorectal cancer (CRC) remain to be fully elucidated. In the present study, the role of PHF8 in the progression of CRC was investigated. The mRNA and protein levels of PHF8 in tissues from patients with CRC and cell lines were detected using the reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Cell viability was analyzed using an MTT assay. The targeted genes were predicted using a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Cell migration was evaluated using a Transwell assay. The results demonstrated that the expression of PHF8 was significantly increased in tumor tissues from patients with CRC and was correlated with tumor‑node‑metastasis stage. In addition, it was found that overexpressed PHF8 was a predictor of poor overall survival rates in patients with CRC. PHF8 loss‑of‑function significantly inhibited proliferation and migration, and promoted apoptosis of CRC cells. In addition, bioinformatics methods demonstrated that PHF8 was a putative target of microRNA (miR)‑488, and miR‑488 was able to inhibit the expression of PHF8 in CRC cells. miR‑488 loss‑of‑function showed increased proliferation and migration, and these effects were reversed by sh‑PHF8 transfection in CRC cells. In vitro and in vivo experiments revealed that PHF8 accelerated cancer cell growth and migration, confirming the oncogenic role of PHF8 in human CRC. In conclusion, PHF8 and miR‑488 may serve as CRC biomarkers for the prediction of clinical outcome and provide a target for the diagnosis and therapy of CRC.
植物同源结构域手指蛋白 8(PHF8)作为一种癌基因,在癌症的发生和发展中得到了强调。然而,其在结直肠癌(CRC)中的临床意义和潜在分子机制仍有待充分阐明。在本研究中,研究了 PHF8 在 CRC 进展中的作用。采用逆转录定量聚合酶链反应和 Western blot 分别检测患者组织和细胞系中 PHF8 的 mRNA 和蛋白水平。采用 MTT 法分析细胞活力。通过生物信息学算法预测靶向基因,并通过双荧光素酶报告基因检测证实。采用 Transwell 检测细胞迁移。结果表明,CRC 患者肿瘤组织中 PHF8 的表达明显增加,与肿瘤-淋巴结-转移分期相关。此外,发现过表达的 PHF8 是 CRC 患者总生存率降低的预测因子。PHF8 功能丧失显著抑制 CRC 细胞的增殖和迁移,并促进细胞凋亡。此外,生物信息学方法表明 PHF8 是 microRNA(miR)-488 的潜在靶点,miR-488 能够抑制 CRC 细胞中 PHF8 的表达。miR-488 功能丧失导致增殖和迁移增加,而在 CRC 细胞中转染 sh-PHF8 可逆转这些作用。体内外实验表明 PHF8 加速了癌细胞的生长和迁移,证实了 PHF8 在人 CRC 中的致癌作用。总之,PHF8 和 miR-488 可能作为 CRC 的生物标志物,用于预测临床结局,并为 CRC 的诊断和治疗提供靶点。