miR-191 promotes tumorigenesis of human colorectal cancer through targeting C/EBPβ.
miR-191 promotes tumorigenesis of human colorectal cancer through targeting C/EBPβ.
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DOI：
10.18632/oncotarget.2864
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发表时间：
2015-02-28
期刊：
影响因子：
--
通讯作者：
Zhang XD
中科院分区：
文献类型：
--
作者：
Zhang XF;Li KK;Gao L;Li SZ;Chen K;Zhang JB;Wang D;Tu RF;Zhang JX;Tao KX;Wang G;Zhang XD
MicroRNA-191（miR-191）是一种小的非编码RNA，参与疾病的发生、癌症的诊断和预后。然而，miR-191如何在结直肠癌中发挥作用仍不清楚。在这项研究中，我们发现miR-191在结肠肿瘤组织中高度表达，并且miR-191的抑制导致异种移植模型中细胞生长，增殖和致瘤性降低。miR-191在结直肠癌细胞系中的过表达改变细胞周期进程和细胞对5-Fu诱导的细胞凋亡的抵抗。机制研究表明，miR-191直接与C/EBPβ mRNA的3′UTR结合，介导C/EBP β mRNA和蛋白表达的降低。我们进一步表明，C/EBPβ诱导结直肠癌细胞系的生长停滞，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。
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.
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