Department of Pathology, State Key Lab of Reproductive Medicine and Cancer Center, Nanjing Medical University, Nanjing, China.
Cell Cycle. 2013 May 1;12(9):1385-94. doi: 10.4161/cc.24477. Epub 2013 Apr 8.
Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Recently, downregulation of microRNA-143 (miR-143) has been observed in CRC tissues. Here in this study, we found that miR-143 expression was downregulated both in CRC patients' blood samples and tumor specimens. MiR-143 expression levels were strongly correlated with clinical stages and lymph node metastasis. Furthermore, insulin-like growth factor-I receptor (IGF-IR), a known oncogene, was a novel direct target of miR-143, whose expression levels were inversely correlated with miR-143 expression in human CRC specimens. Overexpression of miR-143 inhibited cell proliferation, migration, tumor growth and angiogenesis and increased chemosensitivity to oxaliplatin treatment in an IGF-IR-dependent manner. Taken together, these results revealed that miR-143 levels in human blood and tumor tissues are associated with CRC cancer occurrence, metastasis and drug resistance, and miR-143 levels may be used as a new diagnostic marker and therapeutic target for CRC in the future.
结直肠癌(CRC)是世界上主要的癌症相关死亡原因之一。最近,在 CRC 组织中观察到 microRNA-143(miR-143)的下调。在本研究中,我们发现 miR-143 的表达在 CRC 患者的血液样本和肿瘤标本中均下调。miR-143 表达水平与临床分期和淋巴结转移密切相关。此外,胰岛素样生长因子-I 受体(IGF-IR)是一种已知的癌基因,是 miR-143 的一个新的直接靶标,其表达水平与人类 CRC 标本中的 miR-143 表达呈负相关。miR-143 的过表达以 IGF-IR 依赖的方式抑制细胞增殖、迁移、肿瘤生长和血管生成,并增加对奥沙利铂治疗的敏感性。综上所述,这些结果表明,人血液和肿瘤组织中的 miR-143 水平与 CRC 的发生、转移和耐药性有关,miR-143 水平可能在未来作为 CRC 的一种新的诊断标志物和治疗靶点。