Lnc‑RGS5 sponges miR‑542‑5p to promote FoxM1/VEGFA signaling and breast cancer cell proliferation

Abstract

Breast cancer (BRCA) exhibits a high incidence rate among women worldwide. LOC127814295 (ENSG00000232995), termed long non‑coding (lnc)‑regulator of G protein signaling 5 (RGS5), is a novel lncRNA with a genomic region overlapping with protein‑coding gene RGS5. Results obtained using The Cancer Genome Atlas demonstrated that lnc‑RGS5 was deregulated in diverse cancer types, including BRCA; however, the functional role of lnc‑RGS5 remains unclear. Results of the present study demonstrated that lnc‑RGS5 was upregulated in BRCA tissues compared with healthy samples (n=30; P<0.0001), and was associated with the overall survival of patients with triple‑negative BRCA (n=106; P<0.05). Moreover, lnc‑RGS5 expression was significantly higher in triple‑negative BRCA samples than in LumA, LumB, or Her2 subtypes (P<0.05). Functionally, lnc‑RGS5 upregulation promoted BRCA cell proliferation <i>in vitro</i>, whereas lnc‑RGS5 knockdown elicited the opposite function. Stable knockdown of lnc‑RGS5 inhibited tumor cell proliferation <i>in vivo</i>. Bioinformatics analysis revealed that lnc‑RGS5 was significantly associated with RNA binding involved in post‑transcriptional gene silencing (P=0.002). Mechanistically, lnc‑RGS5 functions as a competing endogenous RNA via competitively sponging miR‑542‑5p to upregulate forkhead box M1 (FoxM1) and the VEGFA/Neuropilin 1 axis; thus, promoting BRCA cell proliferation <i>in vitro</i>. Moreover, rescue experiments validated that the lnc‑RGS5/miR‑542‑5p/FoxM1 axis promoted BRCA cell growth <i>in vivo</i>. Collectively, results of the present study demonstrated that lnc‑RGS5 may exhibit potential as a novel oncogenic lncRNA in BRCA. The present study may provide a novel theoretical basis for the role of lncRNA in the targeted therapy of BRCA.