microRNA -140-5p inhibits colorectal cancer invasion and metastasis by targeting ADAMTS5 and IGFBP5Reportar como inadecuado

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Stem Cell Research and Therapy

, 7:180

First Online: 01 December 2016Received: 05 July 2016Revised: 13 October 2016Accepted: 10 November 2016


BackgroundColorectal 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.

MethodsImmunohistochemistry 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.

ResultsmiR-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.

ConclusionsThese 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.

KeywordsColorectal cancer microRNA-140-5p ADAMTS5 IGFBP5 Invasion Metastasis AbbreviationsADAMTSA disintegrin and metalloproteinase with thrombospondin motifs

CRCColorectal cancer

ECMExtracellular matrix

EMTEpithelial-mesenchymal transition

FBSFetal bovine serum

HCCHepatocellular carcinoma

IGFBPInsulin-like growth factor-binding protein


MMDMonocyte to macrophage differentiation-associated

NSCLCNon-small cell lung cancer


PBSPhosphate-buffered saline

qRT-PCRQuantitative real-time polymerase chain reaction

RQRelative quantitation

siRNASmall interfering RNA


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Autor: Lihui Yu - Ying Lu - Xiaocui Han - Wenyue Zhao - Jiazhi Li - Jun Mao - Bo Wang - Jie Shen - Shujun Fan - Lu Wang - Mei 

Fuente: https://link.springer.com/

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