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

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 in vitro, whereas lnc-RGS5 knockdown elicited the opposite function. Stable knockdown of lnc-RGS5 inhibited tumor cell proliferation in vivo. 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 in vitro. Moreover, rescue experiments validated that the lnc-RGS5/miR-542-5p/FoxM1 axis promoted BRCA cell growth in vivo. 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.