BVES-AS1 suppresses the colorectal cancer progression via the miR-1269a/b-SVEP1-PI3K/AKT axis

Adv Clin Exp Med. 2024 Nov;33(11):1217-1236. doi: 10.17219/acem/175050.

Abstract

Background: Numerous studies have indicated the engagement of long non-coding RNA (lncRNA) in various cancer types, including colorectal cancer (CRC). However, the functional and mechanistic roles of lncRNAs in CRC remain largely elusive.

Objectives: The aim of this study was to explore the function and mechanism of lncRNA BVES-AS1 in CRC.

Material and methods: The expression levels of BVES-AS1 were validated in CRC tissues and paired normal samples using quantitative real-time polymerase chain reaction (qPCR) Subsequently, the biological functions of BVES-AS1 in CRC cells were investigated both in vitro and in vivo. Various experimental techniques such as western blot, fluorescence in situ hybridization, RNA-sequencing (RNA-seq), biotin-labeled miRNA pulldown assay, dual-luciferase reporter gene assay, and RNA-protein immunoprecipitation (RIP) assay were employed to elucidate the potential mechanism of BVES-AS1.

Results: The findings of this study demonstrated that BVES-AS1 expression was downregulated in CRC tissues compared to normal tissues, and its expression level was associated with tumor infiltration and tumor-nodule-metastasis (TNM) stage. Furthermore, BVES-AS1 was found to suppress CRC cell proliferation, migration and metastasis both in vitro and in vivo. Mechanistically, BVES-AS1 acted as a sponge for miR-1269a and miR-1269b, thereby regulating SVEP1. Additionally, the silencing of SVEP1 activated the PI3K/AKT pathway.

Conclusions: These results suggest that BVES-AS1 plays a crucial role in the progression of CRC through the miR-1269a/b-SVEP1-PI3K/AKT axis, providing new insights into the therapeutic strategies for CRC.

Keywords: BVES-AS1; PI3K/AKT; SVEP1; colorectal cancer; miRNA.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Signal Transduction

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-akt
  • RNA, Long Noncoding
  • Phosphatidylinositol 3-Kinases
  • MIRN1269 microRNA, human