RNA-binding protein quaking 5 inhibits the progression of non-small cell lung cancer by upregulating netrin-4 expression

It was recently reported that netrin-4 (Ntn-4), 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 Ntn-4 was examined in a public non-small cell lung cancer (NSCLC) dataset from the Netherlands Cancer Institute. This analysis revealed that the mRNA expression level of Ntn-4 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 Ntn-4 was also found to be decreased in NSCLC cells. However, both the function of Ntn-4 and the underlying mechanisms of Ntn-4 downregulation in NSCLC have yet to be fully elucidated. As was anticipated, the overexpression of Ntn-4 led to a marked decrease in the proliferation, migration and invasion of NSCLC cells. Notably, RNA-binding protein quaking 5 (Qki-5) was found to exhibit antitumor activity in lung cancer, not only by enhancing the level of Ntn-4 by binding to Ntn-4 mRNA, but also by suppressing the proliferation, invasion and migration of NSCLC cells. However, Qki-5 is known to be frequently downregulated in NSCLC. Moreover, the knockdown of Ntn-4 was found to reverse the suppressive effects of Qki-5 on NSCLC progression both in vitro and in vivo. Taken together, the findings of the present study demonstrate that Ntn-4 is able to suppress the progression of NSCLC, and that the level of Ntn-4 can be regulated by Qki-5. Therefore, Ntn-4 may be a novel diagnostic and therapeutic target for the treatment of NSCLC.