Alfayez Musaad, Vishnubalaji Radhakrishnan, Alajez Nehad M
Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Anticancer Res. 2016 Oct;36(10):5257-5263. doi: 10.21873/anticanres.11096.
BACKGROUND/AIM: Altered expression of runt-related transcription factor 1 (RUNX1T1) has been observed in several human cancer types; however, the exact role for RUNX1T1 in colorectal cancer (CRC) remains unclear.
The GSE21510 CRC and our previously published datasets were utilized in this study. Gene-expression profiling was conducted using the Agilent microarray platform, while data normalization and bioinformatics were conducted using GeneSpring software. AlamarBlue assay was used to assess cell viability in vitro.
The expression of RUNX1T1 was severely down-regulated in primary CRC and cell lines. Lentiviral-mediated re-expression of RUNX1T1 inhibited CRC cell growth, and global gene-expression analysis revealed the cell cycle, DNA replication, and DNA damage as the pathways most affected by RUNX1T1. Forced expression of RUNX1T1 induced a significant reduction in cellular proliferation and sensitized CRC cells to 5-flurouracil.
Our data revealed a novel role for RUNX1T1 as a tumor-suppressor gene in CRC through modulation of multiple cellular pathways.
背景/目的:在多种人类癌症类型中均观察到 runt 相关转录因子 1(RUNX1T1)表达改变;然而,RUNX1T1 在结直肠癌(CRC)中的确切作用仍不清楚。
本研究使用了 GSE21510 结直肠癌数据集以及我们之前发表的数据集。使用安捷伦微阵列平台进行基因表达谱分析,同时使用 GeneSpring 软件进行数据归一化和生物信息学分析。采用 AlamarBlue 检测法评估体外细胞活力。
RUNX1T1 在原发性结直肠癌和细胞系中的表达严重下调。慢病毒介导的 RUNX1T1 重新表达抑制了结直肠癌细胞生长,全基因表达分析显示细胞周期、DNA 复制和 DNA 损伤是受 RUNX1T1 影响最大的通路。RUNX1T1 的强制表达导致细胞增殖显著减少,并使结直肠癌细胞对 5-氟尿嘧啶敏感。
我们的数据揭示了 RUNX1T1 通过调节多种细胞通路在结直肠癌中作为肿瘤抑制基因的新作用。