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

Int J Oncol. 2023 Oct;63(4):111. doi: 10.3892/ijo.2023.5559. Epub 2023 Aug 18.

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 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.

Keywords: breast cancer; competing endogenous RNA; proliferation; tumorigenesis.

MeSH terms

  • Cell Proliferation / genetics
  • Female
  • Humans
  • MicroRNAs* / genetics
  • RGS Proteins* / genetics
  • RNA, Long Noncoding* / genetics
  • Signal Transduction / genetics
  • Triple Negative Breast Neoplasms*
  • Vascular Endothelial Growth Factor A

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • RGS5 protein, human
  • RGS Proteins
  • MIRN542 microRNA, human

Grants and funding

The present study was supported by Key Research and Development of Social and People's Livelihood (grant nos. cstc2018jscx-mszdX0031 and CSTC510215195605120418).