Sirach E, Bureau C, Péron J M, Pradayrol L, Vinel J P, Buscail L, Cordelier P
INSERM U858, I2MR, Toulouse, France.
Cell Death Differ. 2007 Jun;14(6):1202-10. doi: 10.1038/sj.cdd.4402114. Epub 2007 Mar 9.
Hepatocellular carcinoma (HCC) is a major public health concern because of the absence of early diagnosis and effective treatments. Efficient diagnosis modalities and therapies to treat HCC are needed. Kruppel-like factor (KLF) family members, such as KLF6, are involved in cell proliferation and differentiation. KLF6 is inactivated in solid tumors, which may contribute to pathogenesis. However, KLF6 status in HCC is controversial. Thus, we undertook the characterization of KLF6 expression and function in HCC and HCC-derived cell lines. We found that HCC, HepG2 and HuH7 cells expressed KLF6 messenger ribonucleic acid and protein. Next, using RNA interference, we demonstrated that inhibiting KLF6 expression in vitro strongly impaired cell proliferation-induced G1-phase arrest, inhibited cyclin-dependent kinase 4 and cyclin D1 expression, and subsequent retinoblastoma phosphorylation. Finally, KLF6 silencing caused p53 upregulation and inhibited Bcl-xL expression, to induce cell death by apoptosis. Taken together, these data demonstrated that KLF6 is essential for HCC-derived cells to evade apoptosis.
肝细胞癌（HCC）由于缺乏早期诊断和有效的治疗方法，成为一个主要的公共卫生问题。因此，需要有效的诊断方法和治疗HCC的疗法。Kruppel样因子（KLF）家族成员，如KLF6，参与细胞增殖和分化。KLF6在实体瘤中失活，这可能与发病机制有关。然而，KLF6在HCC中的状态存在争议。因此，我们对KLF6在HCC及HCC衍生细胞系中的表达和功能进行了表征。我们发现，HCC、HepG2和HuH7细胞表达KLF6信使核糖核酸和蛋白质。接下来，我们使用RNA干扰技术证明，在体外抑制KLF6表达会强烈损害细胞增殖诱导的G1期阻滞，抑制细胞周期蛋白依赖性激酶4和细胞周期蛋白D1的表达，以及随后的视网膜母细胞瘤磷酸化。最后，KLF6沉默导致p53上调并抑制Bcl-xL表达，从而通过凋亡诱导细胞死亡。综上所述，这些数据表明KLF6对于HCC衍生细胞逃避凋亡至关重要。
