Wang Hai-Gang, Cao Bin, Zhang Li-Xian, Song Nan, Li Hui, Zhao Wen-Zeng, Li Yan-Shu, Ma Shun-Mao, Yin Dong-Jian
North China Petroleum Bureau General Hospital, Renqiu, Hebei 062552, P.R. China.
Oncol Rep. 2017 Jul;38(1):584-590. doi: 10.3892/or.2017.5708. Epub 2017 Jun 6.
The transcription factor Krüppel-like factor 2 (KLF2) has been shown to function as a tumor suppressor and regulate biological processes of cancer cells, such as cell growth, cell apoptosis and angiogenesis. However, the function and mechanism of KLF2 in colorectal cancer (CRC) is still unknown. In the present study, we show that the expression of KLF2 is diminished in a cohort of CRC cell lines. Also, KLF2 overexpression remarkably inhibits HCT116 and SW480 cell survival and proliferation. Moreover, cell death detection ELISA plus assay showed that KLF2 overexpression increased HCT116 cell proliferation. Caspase-3/7 activity also increased in HCT116 cells transfected with PcDNA3.1-KLF2. Further studies showed that KLF2 significantly suppresses the expression of Notch-1 and is dependent on the decline of the HIF-1α level. Most importantly, silencing Notch-1 expression or HIF-1α level both impair the action of KLF2 overexpression in CRC cells. Collectively, we demonstrated that KLF2 mediates CRC cell biological processes including cell growth and apoptosis via regulating the HIF-1α/Notch-1 signal pathway. These results indicated that KLF2 plays an important role in CRC and provided novel insight on the function of KLF2 in tumor progression.
转录因子Krüppel样因子2（KLF2）已被证明具有肿瘤抑制功能，并可调节癌细胞的生物学过程，如细胞生长、细胞凋亡和血管生成。然而，KLF2在结直肠癌（CRC）中的功能和机制仍不清楚。在本研究中，我们发现KLF2在一组CRC细胞系中的表达降低。此外，KLF2过表达显著抑制HCT116和SW480细胞的存活和增殖。此外，细胞死亡检测ELISA plus分析表明，KLF2过表达增加了HCT116细胞的增殖。在用PcDNA3.1-KLF2转染的HCT116细胞中，Caspase-3/7活性也增加。进一步的研究表明，KLF2显著抑制Notch-1的表达，并且依赖于HIF-1α水平的下降。最重要的是，沉默Notch-1表达或HIF-1α水平均会削弱KLF2过表达在CRC细胞中的作用。总体而言，我们证明KLF2通过调节HIF-1α/Notch-1信号通路介导CRC细胞的生物学过程，包括细胞生长和凋亡。这些结果表明KLF2在CRC中起重要作用，并为KLF2在肿瘤进展中的功能提供了新的见解。
