lncRNA NUTM2A-AS1 Targets the SRSF1/Trim37 Signaling Pathway to Promote the Proliferation and Invasion of Breast Cancer

Abstract

Object. Proliferation and invasion are typical characteristics of breast cancer (BC) cells. Long noncoding RNA NUTM2A-AS1 has been shown to be dysregulated in tumors. This research was to explore the effect of NUTM2A-AS1 on the proliferation and invasion of BC cell lines. Method. Using the tumor database (TCGA) and analysis platform (GEPIA), NUTM2A-AS1 expression in breast cancer cases was compared with the normal cases. In addition, Kaplan-Meier curve of overall survival according to the various levels of NUTM2A-AS1 was assessed. Then, we constructed a knockdown plasmid of NUTM2A-AS1 and successfully reduced the expression function of NUTM2A-AS1 in BC cells. Results. We found NUTM2A-AS1 could promote the malignant phenotype of proliferation and invasion of BC. In terms of mechanism research, NUTM2A-AS1 was mainly located in the cytoplasm of BC cells, which indicated that NUTM2A-AS1 may achieve its function through transcriptional or posttranscriptional regulation pathways. While knocking down NUTM2A-AS1, we detected several major molecules of the trim family. The results showed that only trim37 mRNA was significantly affected, and protein detection also showed that knockdown NUTM2A-AS1 expression could reduce the expression of trim37. The results of RIP experiments suggested that NUTM2A-AS1 played a key role by combining with SRSF1 and affecting the interaction between SRSF1 and trim37 mRNA. The stability test of mRNA also confirmed that during the knockdown of NUTM2A-AS1, the mRNA stability of trim37 decreased significantly, but this downward trend could be reversed by overexpressed SRSF1. The above results suggested that NUTM2A-AS1 could maintain the stability and expression of trim37 through SRSF1 pathway. The results of rescue experiment showed the overexpression of trim37, while knocking down NUTM2A-AS1 could reverse the decrease of proliferation and invasiveness of BC cells induced by NUTM2A-AS1 knockdown. Conclusion. Therefore, trim37 is seen as a necessary target for NUTM2A-AS1 to exert the biological function of BC. Additionally, NUTM2A-AS1 is to regulate the malignant phenotype of BC through NUTM2A-AS1/trim37 pathway.