Abstract
BackgroundMicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 (MACC1) has been newly identified to express highly in colorectal cancer (CRC) and promote tumor metastasis through transactivating metastasis-inducing HGF/MET signaling pathway. In this study, we investigated whether miRNA 143 is involved in the regulation of MACC1 and thus plays a functional role in CRC.ResultsUsing both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3' UTR luciferase reporter gene. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues.ConclusionsOur findings newly described miR-143/MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in western countries [1], with very poor prognosis and high possibilities of tumor invasion and migration
MiR-143 directly targets Metastasis-associated in colon cancer-1 (MACC1) Using online miRNA target prediction databases, we hypothesized that metastasis-associated in colon cancer-1 (MACC1), which has been newly identified as a positive prognostic indicator of metastasis formation in colorectal cancer (CRC) [16], was a target of miR-143 (Figure 2A)
SW480 and SW620 cell lines are derived from the primary colon adenocarcinoma and a node metastasis resected from a single patient respectively [20]
Summary
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in western countries [1], with very poor prognosis and high possibilities of tumor invasion and migration. Growing evidences have supported the cancer-related effects of miRNAs, a newly discovered class a role of tumor suppressor. MiR-143 was validated to inhibit prostate cancer cells proliferation and migration and enhance their sensitivity to docetaxel through suppressing K-RAS [11]. K-RAS and DNMT3A gene were subsequently identified to be regulated by miR143, which partly explained the inhibitory effect of miR143 on CRC growth [13,14]. Studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 (MACC1) has been newly identified to express highly in colorectal cancer (CRC) and promote tumor metastasis through transactivating metastasis-inducing HGF/MET signaling pathway. We investigated whether miRNA 143 is involved in the regulation of MACC1 and plays a functional role in CRC
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