BBOX1-AS1 contributes to colorectal cancer progression by sponging hsa-miR-361-3p and targeting SH2B1

FEBS Open Bio. 2022 May;12(5):983-992. doi: 10.1002/2211-5463.12802. Epub 2022 Mar 26.

Abstract

Colorectal cancer (CRC) is the third main cause of cancer-relevant deaths worldwide, and its incidence has increased in recent decades. Previous studies have indicated that certain long noncoding RNAs (lncRNAs) have regulatory roles in tumor occurrence and progression. Often, lncRNAs are competitive endogenous RNAs that sponge microRNAs to up-regulate mRNAs. Here, we examined the role of a novel lncRNA gamma-butyrobetaine hydroxylase 1 antisense RNA 1 (BBOX1-AS1) in CRC. We observed that BBOX1-AS1 is overexpressed in CRC cell lines, and BBOX1-AS1 knockdown enhances cell proliferation, migration and invasion while reducing cell apoptosis. miR-361-3p is present at a low level in CRC and is negatively modified by BBOX1-AS1. Moreover, miR-361-3p was validated to be targeted by BBOX1-AS1. Src homology 2 B adaptor protein 1 (SH2B1) was notably upregulated in CRC cell lines and was identified as a downstream gene of miR-361-3p. In addition, we found that miR-361-3p amplification can suppress the expression of SH2B1. Finally, data from rescue assays suggested that overexpression of SH2B1 counteracted BBOX1-AS1 silencing-mediated inhibition of CRC progression. In conclusion, BBOX1-AS1 promotes CRC progression by sponging hsa-miR-361-3p and up-regulating SH2B1.

Keywords: BBOX1-AS1; SH2B1; miR-361-3p; colorectal cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Cell Line, Tumor
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • gamma-Butyrobetaine Dioxygenase

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN361 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SH2B1 protein, human
  • BBOX1 protein, human
  • gamma-Butyrobetaine Dioxygenase