Long non-coding RNA BCAR4 aggravated proliferation and migration in esophageal squamous cell carcinoma by negatively regulating p53/p21 signaling pathway

Bioengineered. 2021 Dec;12(1):682-696. doi: 10.1080/21655979.2021.1887645.

Abstract

Long non-coding RNA breast cancer antiestrogen resistance 4 (lncRNA BCAR4) is an independent factor on the survival prognosis of patients with multiple cancers. However, the role of lncRNA BCAR4 in esophageal squamous cell cancer (ESCC) remains unknown. Here, we unraveled that lncRNA BCAR4 was upregulated in ESCC and predicted poor prognosis. Functionally, lncRNA BCAR4 knockdown induced cell apoptosis and G1/S arrest, while inhibited cell proliferation and migration in vitro; conversely, overexpressing lncRNA BCAR4 promoted proliferation and metastasis. Mechanistically, lncRNA BCAR4 sponged miR-139-3p to upregulate ELAVL1, thereby inhibiting p53/p21 pathway in ESCC cells. In conclusion, lncRNA BCAR4 promotes ESCC tumorigenesis via regulating p53/p21 signaling pathway and develops a brand-new biomarker and medicine target for ESCC.

Keywords: ELAVL1; ESCC; LncRNA BCAR4; miR-139-3p; p53/p21 signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / mortality
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / metabolism
  • Esophageal Squamous Cell Carcinoma* / mortality
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Signal Transduction / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • BCAR4 non-coding RNA, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53

Grants and funding

National Natural Science Foundation of China (81702872 to S.Y. and 81702942 to B.L.), Shanghai Natural Science Fund Project (Grant no. 19ZR1449000), General Program of Shanghai Municipal Commission of Health and Family Planning (No. 20174Y0095) provide finance foundation to authors.