Abstract
Accumulating evidences have shown microRNAs (miRNAs) play important roles in the progression of human cancers including colorectal cancer (CRC). However, the biological function and molecular mechanism of miRNAs in CRC still remains to be further investigated. Using microarray, we found and confirmed that miR-208a-3p was up-regulated in CRC tissues. Its high expression was statistically associated with distant metastasis and TNM stage. Functional assays revealed inhibition of miR-208a-3p suppressed proliferation, invasion and migration, and induced cell apoptosis of CRC cells. Moreover, we identified programmed cell death protein 4 (PDCD4), a well-known tumor suppressor, is a direct target of miR-208a-3p. We also found that overexpression of PDCD4 suppressed cell proliferation, invasion, and migration. Importantly, silencing of PDCD4 efficiently abrogated the promoting effects on CRC cells proliferation, invasion, and migration caused by inhibition of miR-208a-3p. Our findings confirmed the oncogenic role of miR-208a-3p via targeting PDCD4 in CRC, identifying miR-208a-3p as a potential diagnosis and therapeutic biomarker for CRC.
Highlights
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and the third leading cause of cancer-related deaths worldwide [1]
MiR-208a-3p was up-regulated in human CRC tissues and cell lines, and associated with distant lymph node metastasis and tumor node metastasis (TNM) stage of CRC
Further experiments indicated that the effect of miR-208a-3p on CRC cell proliferation, invasion, and migration was mediated by targeting programmed cell death protein 4 (PDCD4)
Summary
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and the third leading cause of cancer-related deaths worldwide [1]. Ge et al [10] showed that miR-196a and miR-196b expressions are frequently up-regulated in CRC tissues and to be associated with clinical stages and survival progression. Xu et al [11] showed that miR-149 plays an important role in suppressing tumor initiation and progression of CRC by directly targeting forkhead box transcription factor FOXM1. Jiao et al [12] showed that miR-4261 acted as a tumor suppressor and could cause a significant decrease in tumor cell metastasis in vitro and tumor growth in a nude mouse xenograft model. These indicate that miRNAs might play a crucial role in the progression of CRC. The roles of many other aberrantly expressed miRNAs in CRC development are still unknown
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