LncRNA BBOX1-AS1 Contributes to the Progression of Esophageal Carcinoma by Targeting the miR-361-3p/COL5A1 Axis

Biochem Genet. 2023 Aug;61(4):1351-1368. doi: 10.1007/s10528-022-10307-3. Epub 2022 Dec 31.

Abstract

Long noncoding RNAs (lncRNAs) are known to participate in the progression of several cancers, including esophageal carcinoma (EC), a common malignancy of the digestive system. Although the role of the lncRNA-miRNA-mRNA regulatory network is crucial for the growth and progression of EC, the regulation of lncRNA BBOX1-AS1 (BBOX1 antisense RNA1) remains unclear. We performed reverse transcription-quantitative PCR (RT-qPCR) and western blotting to evaluate miR-361-3p, collagen type V alpha 1 chain (COL5A1), and BBOX1-AS1 expression levels in EC cells and tissues. The colony formation assay (CFA) and Cell Counting Kit-8 (CCK-8) were employed to identify EC cell proliferation, while western blotting was used to examine EC cell apoptosis and Bax and Bcl-2 expression levels. The effect of BBOX1-AS1 on EC proliferation was determined using an in vivo carcinogenesis assay. Correlation between COL5A1, BBOX1-AS1, and miR-361-3p was examined using the luciferase reporter system and RNA immunoprecipitation assay (RIP). Herein, we observed that BBOX1-AS1 expression levels were upregulated in EC cells and tissues. BBOX1-AS1 knockdown inhibited EC cell proliferation and conferred a pro-apoptotic effect. These results indicated a positive interaction between BBOX1-AS1 and miR-361-3p in EC and a negative association with miR-361-3p. COL5A1 was recognized as a downstream miR-361-3p target and was inversely related to miR-361-3p in EC. Therefore, BBOX1-AS1 expression suppressed cell apoptosis and promoted cell proliferation via the downregulation of miR-361-3p and upregulation of COL5A1 expression. Overall, BBOX1-AS1 facilitates EC progression via the miR-361-3p or COL5A1 axis, indicating that BBOX1-AS1 might be a potential therapeutic target for EC therapy.

Keywords: AS1; Apoptosis; COL5A1; Esophageal carcinoma; LncRNA BBOX1; miR-361-3p.

MeSH terms

  • Carcinoma* / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Collagen / metabolism
  • Collagen Type V / genetics
  • Collagen Type V / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • Collagen
  • COL5A1 protein, human
  • Collagen Type V
  • MIRN361 microRNA, human