Insulin receptor substrate-1 and dishevelled 2 are negatively regulated by microRNA-144 and inhibit nasopharyngeal carcinoma cell malignancy

Insulin receptor substrate-1 (IRS-1) is reported to play a critical role in the development, progression, invasion and metastasis of several types of tumors and is abnormally expressed in nasopharyngeal carcinoma (NPC). Although IRS-1 is predicted to be targeted by microRNA (miR)-144, the biological roles and potential mechanisms of miR-144 in NPC remain unclear. In the present study, the expression levels of miR-144 and IRS-1 in several NPC cell lines were first examined, and found that they were negatively correlated. Following the introduction of the miR-144 mimic, IRS-1 was downregulated at the protein level without affecting the mRNA level. The Cell Counting Kit-8 assay showed that the miR-144 mimic and siRNA targeting IRS-1 mRNA significantly decreased cell proliferation by arresting the cell cycle at the G(1)/G(0) phase. The malignant behaviours of NPC cell lines, including migration, invasion and tumour formation in soft agar, were then analyzed after regulating miR-144 levels; as expected, the results showed that both the miR-144 mimic and siIRS-1 decreased these malignant behaviours. Furthermore, the downregulation of IRS-1 by miR-144 decreased the expression level of dishevelled 2 (Dvl2) protein without affecting its mRNA level, and Dvl2 overexpression abolished the inhibitory effect of the miR-144 mimic in NPC, indicating that miR-144 potentially regulates NPC by indirectly regulating Dvl2. Taken together, the present study results suggest that miR-144 acts as a tumour suppressor in NPC cell lines by regulating IRS-1 and Dvl2, which indicates that it is a potential therapeutic target for NPC treatment.