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MicroRNA-143 抑制结直肠癌的肿瘤生长和血管生成,并增强对奥沙利铂的化疗敏感性。

MicroRNA-143 inhibits tumor growth and angiogenesis and sensitizes chemosensitivity to oxaliplatin in colorectal cancers.

机构信息

Department of Pathology, State Key Lab of Reproductive Medicine and Cancer Center, Nanjing Medical University, Nanjing, China.

出版信息

Cell Cycle. 2013 May 1;12(9):1385-94. doi: 10.4161/cc.24477. Epub 2013 Apr 8.

Abstract

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.

摘要

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。

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