Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Gynecol Oncol. 2012 Jan;124(1):125-33. doi: 10.1016/j.ygyno.2011.09.026. Epub 2011 Oct 19.
Increased expression of miR-200c was recently reported in endometrial carcinoma compared with normal tissues. In this study, we evaluated the role of miR-200c in cell growth and drug sensitivity in endometrial carcinoma and investigated the underlying mechanisms.
The expression of miR-200c in human endometrial tissues was detected by quantitative RT-PCR. The transfection with anti-miRNA (anti-miR) or the premature form of miRNA (pre-miR) was performed to regulate the level of expression of miRNA-200c in endometrial carcinoma cells, HEC-1A and Ishikawa. To identify the target genes for miR-200c, we performed mRNA microarray after pre-miR-200c transfection in HEC-1A cells.
We found that miR-200c expression was increased in endometrial carcinoma compared with normal endometrial tissues. Anti-miR or pre-miR-200c could regulate cell survival, proliferation, and apoptosis and affect cytotoxicity in endometrial cancer cells. Through mRNA microarray analysis, we found that miR-200c inhibits the expression of BRD7, which was recently reported as a potential tumor suppressor gene. MiR-200c regulated the translocation of β-catenin from the cytoplasm to the nucleus via inhibition of BRD7, resulting in increased expression of its transcriptional target genes, cyclinD1 and c-myc.
The interaction between miR-200c and BRD7 might have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer.
最近的研究报道，miR-200c 在子宫内膜癌组织中的表达高于正常组织。本研究评估了 miR-200c 在子宫内膜癌中的细胞生长和药物敏感性中的作用，并探讨了其潜在的机制。
通过定量 RT-PCR 检测人子宫内膜组织中 miR-200c 的表达。通过反义 miRNA（anti-miR）或 miRNA 前体（pre-miR）转染来调节子宫内膜癌细胞（HEC-1A 和 Ishikawa）中 miR-200c 的表达水平。为了鉴定 miR-200c 的靶基因，我们在 HEC-1A 细胞中转染 pre-miR-200c 后进行了 mRNA 微阵列分析。
我们发现，与正常子宫内膜组织相比，miR-200c 在子宫内膜癌中的表达增加。Anti-miR 或 pre-miR-200c 可调节细胞存活、增殖和凋亡，并影响子宫内膜癌细胞的细胞毒性。通过 mRNA 微阵列分析，我们发现 miR-200c 抑制 BRD7 的表达，BRD7 最近被报道为一种潜在的肿瘤抑制基因。miR-200c 通过抑制 BRD7 使β-catenin 从细胞质易位到细胞核，导致其转录靶基因 cyclinD1 和 c-myc 的表达增加。
miR-200c 和 BRD7 之间的相互作用可能在控制子宫内膜癌细胞的生长中具有重要作用，并提示了治疗这种癌症的新的靶向途径。
