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

Lihui Yu,Jun Mao,Mei Wang,Lianhong Li,Xiaocui Han,Wenyue Zhao,Bo Wang,Lu Wang,Jianwu Tang,Jiazhi Li,Bo Song,Shujun Fan,Ying Lu,Jie Shen

doi:10.1186/s13287-016-0438-5

Abstract

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.

Highlights

Colorectal cancer (CRC) is one of the most common malignancies in the world. microRNA-140-5p has been shown to be involved in cartilage development and osteoarthritis (OA) pathogenesis
Results miR-140 expression is reduced in the CRC specimens, and its downregulation is associated with the tumor stage and metastasis To determine the role of miR-140 in CRC development and progression, we evaluated the expressions of miR140 in 60 paired CRC specimens and the corresponding normal colorectal tissues using quantitative real-time polymerase chain reaction (qRT-PCR) analysis
We found that miR-140 inhibited the protein expressions (Fig. 2c) and decreased the messenger RNAs (mRNAs) levels of ADAMTS5 and IGFBP5 (Fig. 2d) in both HCT116 and RKO cells compared to the negative controls

Summary

Introduction

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. Colorectal cancer (CRC) is one of the most common malignancies and the second most common cause of cancer deaths worldwide [1, 2]. The development of CRC is a multistep progression involving the activation of oncogenes and inactivation of tumor suppressor genes, which will affect all aspects of tumorigenicity of CRC, such as cell proliferation, apoptosis, invasion, and metastasis [4]. Abnormal expression of miRNAs is suggested to be associated with various human disorders, including cancer, indicating that they play a critical role in the molecular mechanism of cancer pathogenesis and progression [7]

Methods

Results

Conclusion