lncRNA BCAR4 sponges miR‑370‑3p to promote bladder cancer progression via Wnt signaling

Int J Mol Med. 2020 Feb;45(2):578-588. doi: 10.3892/ijmm.2019.4444. Epub 2019 Dec 27.

Abstract

Accumulating evidence suggests that the aberrant expression of long non‑coding RNAs (lncRNAs) is involved in the initiation, development and metastasis of bladder cancer (BC). Although several differentially expressed lncRNAs have been identified via lncRNA expression profiling of BC tissues, their functions and the molecular mechanisms underlying these functions remain to be fully elucidated. In the present study, elevated levels of lncRNA breast cancer anti‑estrogen receptor 4 (BCAR4) were identified in BC tissues compared with matched healthy tissues. Silencing of BCAR4 inhibited cell proliferation and induced apoptosis in BC cell lines 5637 and T24. Downregulation of BCAR4 led to the inactivation of Wnt signaling. Mechanistically, BCAR4 directly sponged microRNA (miR)‑370‑3p and elevated Wnt7a expression. Endogenous expression of Wnt7a reversed BCAR4 silencing‑mediated cell growth arrest and induction of apoptosis in BC cells accompanied with a re‑activation of Wnt signaling. Reverse transcription‑quantitative PCR indicated that there was a strong association between BCAR4, miR‑370‑3p and Wnt7a expression in tumors from patients with BC compared with healthy control tissues. In conclusion, results of the present study suggest that lncRNA BCAR4 promoted proliferation and survival of BC cells via downregulation of miR‑370‑3p. Therefore, lncRNA BCAR4 may be a lncRNA of oncogenic potential in BC.

Keywords: ncRNA BcAR4; Wnt signaling; bladder cancer; miR-370-3p.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Wnt Signaling Pathway*

Substances

  • BCAR4 non-coding RNA, human
  • MIRN370 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding