BBOX1-AS1 Accelerates Gastric Cancer Proliferation by Sponging miR-3940-3p to Upregulate BIRC5 Expression

Dig Dis Sci. 2021 Apr;66(4):1054-1062. doi: 10.1007/s10620-020-06308-0. Epub 2020 May 11.

Abstract

Background: Gastric cancer (GC) is one type of the most general malignancies in the globe. Research increasingly suggests long non-coding RNAs (lncRNAs) exert crucial roles in GC. However, the function of BBOX1-AS1 in GC has not been reported yet, it needs more explorations.

Aims: The aim of the study is to figure out the role and related regulation mechanism of BBOX1-AS1 in GC.

Methods: RT-qPCR assay was applied to detect genes expression. The role of BBOX1-AS1 in GC was investigated by cell counting kit-8, colony formation, tunel detection, and western blot assays. The binding ability between miR-3940-3p and BBOX1-AS1 (or BIRC5) by RIP, RNA pull-down and luciferase reporter assays.

Results: The expression of BBOX1-AS1 presented significantly upregulation in GC tissues and cells. Moreover, upregulation of BBOX1-AS1 promoted GC cell proliferation, and inhibited GC cell apoptosis. However, downregulation of BBOX1-AS1 led to opposite results. Furtherly, we discovered that BBOX1-AS1 bound with miR-3940-3p and also negatively regulated miR-3940-3p. Besides, it proved that miR-3940-3p interplayed with BIRC5 and negatively regulated BIRC5. Through rescue experiments, we proved that BIRC5 reversed miR-3940-3p-mediated cell proliferation or apoptosis in BBOX1-AS1-dysregulated GC cells.

Conclusions: BBOX1-AS1 accelerates GC proliferation by sponging miR-3940-3p to upregulate BIRC5 expression, which may guide a new direction into the therapeutic strategies of GC.

Keywords: BBOX1-AS1; BIRC5; Gastric cancer; miR-3940-3p.

Publication types

  • Retracted Publication

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Survivin / genetics*
  • Transcription Factors
  • Transcriptional Activation
  • Up-Regulation
  • gamma-Butyrobetaine Dioxygenase / genetics*

Substances

  • BIRC5 protein, human
  • MIRN3940 microRNA, human
  • MicroRNAs
  • Survivin
  • Transcription Factors
  • BBOX1 protein, human
  • gamma-Butyrobetaine Dioxygenase