Abstract
MicroRNAs (miRNAs) play a critical role in controlling tumor invasion and metastasis via regulating the expression of a variety of targets, which act as oncogenes or tumor suppressor genes. Abnormally expressed miR-625-3p has been observed in several types of human cancers. However, the molecular mechanisms of miR-625-3p-mediated tumorigenesis are largely elusive. Therefore, the aim of this study was to evaluate the biological function and molecular insight on miR-625-3p-induced oncogenesis in colorectal carcinoma (CRC). The effects of miR-625-3p in cell migration and invasion were analyzed by wound healing assay and transwell assay, respectively. In addition, the expression of miR-625-3p and its targets was detected in five human CRC cell lines. In the present study, we found that overexpression of miR-625-3p promoted migration and invasion in SW480 cells, whereas downregulation of miR-625-3p inhibited cell motility in SW620 cells. More importantly, we observed potential binding sites for miR-625-3p in the 3'-untranslated region of suppressor of cancer cell invasion (SCAI). Notably, we identified that overexpression of miR-625-3p inhibited the expression of SCAI, while depletion of miR-625-3p increased SCAI level, suggesting that SCAI could be a target of miR-625-3p. Additionally, we revealed that miR-625-3p exerts its oncogenic functions through regulation of SCAI/E-cadherin/MMP-9 pathways. Our findings indicate the pivotal role of miR-625-3p in invasion that warrants further exploration whether targeting miR-625-3p could be a promising approach for the treatment of CRC.
Highlights
Colorectal cancer (CRC) is the third most common tumor and the primary cause of cancer-related death worldwide [1]
Our results indicated that miR-625-3p could promote cell invasion in CRC cells
We explored the molecular mechanism of miR-625-3p-meidated tumorigenesis in CRC cells
Summary
Colorectal cancer (CRC) is the third most common tumor and the primary cause of cancer-related death worldwide [1]. Recent accumulating evidence suggests that microRNAs (miRNAs) play a critical role in the www.impactjournals.com/oncotarget regulation of multiple cellular processes during cancer development and progression, including tumor invasion and metastasis [3, 4]. Investigating tumor-specific miRNAs and their targets is critical to understand their role in tumorigenesis and to identify new molecular markers for the diagnosis, prognosis, and treatment of CRC. These findings further indicate that targeting miRNAs could be useful for treating human cancers with aberrant miRNAs expression [13, 14]
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