Zhang Xiao-Fei, Li Ke-ke, Gao Lu, Li Shang-Ze, Chen Ke, Zhang Jun-Bin, Wang Di, Tu Rong-Fu, Zhang Jin-Xiang, Tao Kai-Xiong, Wang Guobin, Zhang Xiao-Dong
College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, PR China.
Oncotarget. 2015 Feb 28;6(6):4144-58. doi: 10.18632/oncotarget.2864.
MicroRNA-191 (miR-191), a small non-coding RNA, is involved in disease development and cancer diagnosis and prognosis. However, how miR-191 functions in colorectal cancer remains largely unclear. In this study, we show that miR-191 is highly expressed in colon tumor tissues, and that inhibition of miR-191 leads to decreased cell growth, proliferation and tumorigenicity in a xenograft model. Overexpression of miR-191 in colorectal cancer cell lines alters cell cycle progression and cell resistance to 5-Fu induced cell apoptosis. Mechanistic studies demonstrated that miR-191 directly binds to the 3'UTR of the C/EBPβ mRNA and mediates a decrease in the mRNA and protein expression of C/EBPβ. We further showed that C/EBPβ induces growth arrest in a colorectal cancer cell line and that its expression is negatively correlated with the miR-191 level in patient samples. Our findings suggest that miR-191 may be a potential gene therapy target for the treatment of colorectal cancer.
微小RNA - 191(miR - 191)是一种小型非编码RNA,参与疾病发展以及癌症的诊断和预后。然而,miR - 191在结直肠癌中如何发挥作用仍不清楚。在本研究中,我们发现miR - 191在结肠肿瘤组织中高表达,并且在异种移植模型中抑制miR - 191会导致细胞生长、增殖及致瘤性降低。在结直肠癌细胞系中过表达miR - 191会改变细胞周期进程以及细胞对5 - 氟尿嘧啶诱导的细胞凋亡的抗性。机制研究表明,miR - 191直接结合C/EBPβ mRNA的3'UTR,并介导C/EBPβ的mRNA和蛋白表达降低。我们进一步表明,C/EBPβ在结直肠癌细胞系中诱导生长停滞,并且其表达与患者样本中的miR - 191水平呈负相关。我们的研究结果表明,miR - 191可能是治疗结直肠癌的潜在基因治疗靶点。