RESUMEN
It was recently reported that netrin4 (Ntn4), a component of the extracellular matrix, when downregulated, is involved in the progression of several types of cancer, including breast cancer, colorectal tumours, neuroblastoma and gastric cancer. In the present study, the level of Ntn4 was examined in a public nonsmall cell lung cancer (NSCLC) dataset from the Netherlands Cancer Institute. This analysis revealed that the mRNA expression level of Ntn4 was lower in the samples of patients with NSCLC compared with that in the control samples. Consistent with the mRNA level, the protein level of Ntn4 was also found to be decreased in NSCLC cells. However, both the function of Ntn4 and the underlying mechanisms of Ntn4 downregulation in NSCLC have yet to be fully elucidated. As was anticipated, the overexpression of Ntn4 led to a marked decrease in the proliferation, migration and invasion of NSCLC cells. Notably, RNAbinding protein quaking 5 (Qki5) was found to exhibit antitumor activity in lung cancer, not only by enhancing the level of Ntn4 by binding to Ntn4 mRNA, but also by suppressing the proliferation, invasion and migration of NSCLC cells. However, Qki5 is known to be frequently downregulated in NSCLC. Moreover, the knockdown of Ntn4 was found to reverse the suppressive effects of Qki5 on NSCLC progression both in vitro and in vivo. Taken together, the findings of the present study demonstrate that Ntn4 is able to suppress the progression of NSCLC, and that the level of Ntn4 can be regulated by Qki5. Therefore, Ntn4 may be a novel diagnostic and therapeutic target for the treatment of NSCLC.