microRNA -140-5p inhibits colorectal cancer invasion and metastasis by targeting ADAMTS5 and IGFBP5

Abstract

Background: Colorectal cancer (CRC) is one of the most common malignancies in the world. microRNA-140-5p (miR-140) has been shown to be involved in cartilage development and osteoarthritis (OA) pathogenesis. Some contradictions still exist concerning the role of miR-140 in tumor progression and metastasis, and the underlying mechanism is uncertain. Methods: Immunohistochemistry was performed to determine the expressions of ADAMTS5 and IGFBP5 in CRC tissues. Human CRC cell lines HCT116 and RKO were transfected with miR-140 mimic, inhibitor, or small interfering RNA (siRNA) against ADAMTS5 or IGFBP5, respectively, using oligofectamine or lipofectamine 2000. Scratch-wound assay and transwell migration and invasion assays were used to evaluate the effects of miR-140 on the capabilities of migration and invasion. The levels of miR-140 and ADAMTS5 and IGFBP5 mRNA were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was performed to examine the expression of ADAMTS5 and IGFBP5 proteins. Results: miR-140 was significantly reduced, whereas ADAMTS5 and IGFBP5 were upregulated, in the human CRC tissues compared to the corresponding normal colorectal mucosa. miR-140 downregulation and ADAMTS5 or IGFBP5 overexpression were associated with the advanced TNM stage and distant metastasis of CRC. There was a reverse correlation between miR-140 levels and ADAMTS5 and IGFBP5 expression in CRC tissues. ADAMTS5 and IGFBP5 were downregulated by miR-140 at both the protein and mRNA levels in the CRC cell lines. The gain-of- and loss-of-function studies showed that miR-140 inhibited CRC cell migratory and invasive capacities at least partially via downregulating the expression of ADAMTS5 and IGFBP5. Conclusions: These findings suggest that miR-140 suppresses CRC progression and metastasis, possibly through downregulating ADAMTS5 and IGFBP5. miR-140 might be a potential therapeutic candidate for the treatment of CRC.