Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
Med Oncol. 2012 Sep;29(3):1681-6. doi: 10.1007/s12032-011-0085-8. Epub 2011 Oct 13.
Recently, accumulating evidence indicates that dysregulation of miRNAs is associated with the initiation and progression of cancer. MiR-101 has been reported down-regulated in various types of cancer. The aim of this study was to investigate the expression profile of miR-101 and its target gene Mcl-1 in NSCLC and to assess their clinical significance. QRT-PCR was used in the detection of miR-101 and Mcl-1 mRNA expression both in NSCLC tissue and in adjacent normal lung tissue. Immunohistochemistry and Western blot analysis were used in the detection of Mcl-1 protein expression. The clinicopathological implications of these molecules were analyzed statistically. Survival analysis was performed to assess prognostic significance. Down-regulation of miR-101 was associated with overexpression of Mcl-1 mRNA in NSCLC tissue when compared with corresponding normal tissue, with a negative correlation (r = -0.724, P < 0.01). MiR-101 expression was significantly associated with pathological stage (P = 0.004) and lymph node involvement (P = 0.012). Overexpression of Mcl-1 was associated with pathological grade (P = 0.022) and lymph node involvement (P = 0.017). A comparison of survival curves of low versus high expressers of miR-101 and Mcl-1 revealed a highly significant difference in NSCLC (P < 0.05), which suggests that reduced expression of miR-101 versus overexpression of Mcl-1 is associated with a poorer prognosis. Our results suggest that down-regulation of miR-101 may result in enhanced expression of Mcl-1 in NSCLC, which consequently favored tumor progression. MiR-101 and Mcl-1 may play important roles as biomarkers for prognosis and therapeutic targets in NSCLC.
最近，越来越多的证据表明 miRNA 的失调与癌症的发生和发展有关。miR-101 在各种类型的癌症中都被报道下调。本研究旨在研究 miR-101 及其靶基因 Mcl-1 在 NSCLC 中的表达谱，并评估其临床意义。QRT-PCR 用于检测 NSCLC 组织和相邻正常肺组织中 miR-101 和 Mcl-1 mRNA 的表达。免疫组织化学和 Western blot 分析用于检测 Mcl-1 蛋白表达。这些分子的临床病理意义进行了统计学分析。生存分析用于评估预后意义。与相应的正常组织相比，NSCLC 组织中 miR-101 的下调与 Mcl-1 mRNA 的过表达相关，呈负相关(r=-0.724，P<0.01)。miR-101 的表达与病理分期(P=0.004)和淋巴结受累(P=0.012)显著相关。Mcl-1 的过表达与病理分级(P=0.022)和淋巴结受累(P=0.017)相关。miR-101 和 Mcl-1 低表达与高表达者的生存曲线比较显示 NSCLC 有显著差异(P<0.05)，这表明 miR-101 表达降低与 Mcl-1 过表达与预后不良相关。我们的结果表明，miR-101 的下调可能导致 NSCLC 中 Mcl-1 的表达增强，从而有利于肿瘤的进展。miR-101 和 Mcl-1 可能作为 NSCLC 预后的生物标志物和治疗靶点发挥重要作用。
