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

• Published in: Cell cycle (Georgetown, Tex.) Vol. 12; no. 9; pp. 1385 - 1394
• Main Authors: Qian, Xu, Yu, Jing, Yin, Yu, He, Jun, Wang, Ling, Li, Qi, Zhang, Lou-Qian, Li, Chong-Yong, Shi, Zhu-Mei, Xu, Qing, Li, Wei, Lai, Li-Hui, Liu, Ling-Zhi, Jiang, Bing-Hua
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.05.2013; Landes Bioscience
• Subjects: angiogenesis; Animals; Base Sequence; Cell Line, Tumor; Cell Movement - drug effects; Cell Movement - genetics; Cell Proliferation - drug effects; chemotherapy; Colorectal Neoplasms - blood supply; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Down-Regulation - drug effects; Down-Regulation - genetics; Gene Expression Regulation, Neoplastic - drug effects; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; IGF-IR; Mice; Mice, Nude; microRNA-143; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Sequence Data; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - genetics; Organoplatinum Compounds - pharmacology; Organoplatinum Compounds - therapeutic use; Receptor, IGF Type 1 - metabolism; tumorigenesis; Vascular Endothelial Growth Factor A - metabolism; microRNA-143; tumorigenesis; IGF-IR; chemotherapy; angiogenesis
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.24477

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.