Abstract
Colorectal cancer (CRC) is one of the most common prevalent cancer types worldwide. MicroRNAs (miRNAs or miRs) have been demonstrated to play crucial roles in the development, metastasis and drug resistance of CRC. In the present study, a strikingly elevated expression of miR-552 was determined in CRC tumor tissues and cells by a miRNA profiling analysis. Importantly, the gene of A Disintegrin And Metalloprotease (ADAM) family member 28 (ADAM28) was identified as a target of miR-552, which was further validated in terms of genetic dual luciferase report assay. Furthermore, an inhibition of miR-552 in LOVE and LS174T CRC cells by transducing miR-552 inhibitor (antagomiR-552) with a lentiviral vector exhibited an ability to reduce cell proliferation, migration and clonogenicity. Moreover, both LOVO and LS174T cells stably expressing miR-552 inhibitor displayed a decreased ability to develop tumors in a murine xenograft model in vivo. In contrast, a knockdown of ADAM28 by short hairpin RNA could reverse the antagomiR-552-induced inhibition of metastatic features of CRC cells in vitro. These results suggested that miR-552 is an oncomir able to promote CRC metastasis in part through a mechanism of targeting ADAM28, which may be a novel target for CRC treatment and warrants for further investigation.
Highlights
MicroRNAs are a family of 18–22 nt small non-coding RNAs that negatively regulate the gene expressions of target mRNAs at the post-transcriptional level through a non-genetically mutational mechanism
In order to further validate a correlation of the expression of these miRNAs and clinicopathologic stages in Colorectal cancer (CRC), the relative expression of miR-552 and miR-592 in CRC tumor tissues and cell lines was evaluated by a Quantitative reverse transcription-PCR (qRT-PCR) assay (Figure 1 and Table 1)
We identified miR-552 and miR-592 were potential oncogenes in CRC, in which both miR-552 and miR-592 were significantly evoked in CRC, which were correlated with the TNM stages and lymph node metastasis of this type of cancer
Summary
MicroRNAs (miRNAs) are a family of 18–22 nt small non-coding RNAs that negatively regulate the gene expressions of target mRNAs at the post-transcriptional level through a non-genetically mutational mechanism. To date, accumulating evidence has demonstrated the importance of miRNAs in cancer development and progression In this regard, the dysregulated miRNAs have been involved in the regulation of gene function that contributed to the initiation, growth, metastasis, recurrence and acquisition of drug-resistance in a variety of cancers, including the colorectal cancer (CRC). Recent miRNA profiling studies have demonstrated alterations of miRNA expression in tumors compared to paired adjacent normal tissues in CRC, which has been proposed to correlate with the stages and metastasis in CRC patients In this context, miRNAs can play a functionality of either tumor-suppressors or oncogenes (oncomirs) through mechanisms of directly targeting genes in the key steps of initial and metastatic processes, as well as acquired drug-resistances [6,7,8]
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