LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma.

Abstract

La-related protein1 (LARP1) is a conserved RNA-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Dysregulated LARP1 has been reported to be related to the development of several cancers. However, the exact function and mechanism of LARP1 in non-small cell lung cancer (NSCLC) is largely unknown. In the present study, we found that the mRNA levels of LARP1 were increased in NSCLC cells compared to those in normal control cells. Knockdown of LARP1 inhibited cell proliferation, migration and invasion in NSCLC cells and tumourigenicity in H520 cells. Both invitro and invivo analyses confirmed that STAT3 signalling was inactivated by the knockdown of LARP1. Moreover, LARP1 was identified as a direct target of miR-374a. Overexpression of miR-374a attenuated the promotor effects of LARP1 by inhibiting proliferation, metastasis and STAT3 signalling. Clinically, LARP1 was markedly overexpressed in NSCLC tissues, and upregulated LARP1 was correlated with tumour progression and poor survival. The expression of miR-374a was negatively correlated with the expression of LARP1 in NSCLC tissues. Furthermore, we found that XIST functioned as a competing endogenous RNA to suppress miR-374a, which regulated its downstream target LARP1. In summary, we suggest that the dysfunction of the XIST/miR-374a/LARP1 axis contributes to NSCLC and may serve as a promising therapeutic strategy for treatment.