Regulation of the β‑catenin/LEF‑1 pathway by the siRNA knockdown of RUVBL1 expression inhibits breast cancer cell proliferation, migration and invasion

Oncol Rep. 2025 Feb;53(2):22. doi: 10.3892/or.2024.8855. Epub 2024 Dec 13.

Abstract

RUVBL1 is a protein characterized by its DNA‑dependent ATPase activity and DNA deconjugating enzyme function. It is a member of the ATPase (AAA+) protein family associated with various cellular processes. Available research confirms that the expression of RUVBL1 is upregulated in breast cancer (BRCA) cell lines; however, the mechanisms underlying its functional role in BRCA remain unclear. The β‑catenin/lymphoid enhancer factor‑1 (LEF‑1) pathway plays a crucial role in the occurrence and development of BRCA. The aim of the present study was to investigate whether RUVBL1 regulates the proliferation, migration and invasion of BRCA cells by participating in the β‑catenin/LEF‑1 signaling pathway. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis were employed to compare the RUVBL1 expression levels between normal mammary epithelial cells (MCF‑10a) and BRCA cell lines (MDA‑MB‑231 and MCF‑7). Scratch, Cell Counting Kit‑8 and Transwell assays were utilized to assess the effects of RUVBL1 knockdown on the proliferation, migration and invasion of BRCA cells. Following the downregulation of RUVBL1 expression in vitro, western blot analysis and RT‑qPCR were conducted to investigate its role in regulating the β‑catenin/LEF‑1 pathway. The aforementioned experiments proved that the knockdown of RUVBL1 expression inhibited BRCA cell proliferative, migratory and invasive capabilities, modulating the β‑catenin/LEF‑1 pathway. Collectively, the findings of the present study provide preliminarily confirmation that RUVBL1 participates in the molecular mechanisms of the β‑catenin signaling pathway, which may provide a novel target for BRCA treatment.

Keywords: RUVBL1; breast cancer; invasion; migration; proliferation; β‑catenin/lymphoid enhancer factor‑1.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities* / genetics
  • ATPases Associated with Diverse Cellular Activities* / metabolism
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation* / genetics
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Lymphoid Enhancer-Binding Factor 1* / genetics
  • Lymphoid Enhancer-Binding Factor 1* / metabolism
  • MCF-7 Cells
  • Neoplasm Invasiveness* / genetics
  • RNA, Small Interfering* / genetics
  • Signal Transduction
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • ATPases Associated with Diverse Cellular Activities
  • beta Catenin
  • RUVBL1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • RNA, Small Interfering
  • CTNNB1 protein, human
  • LEF1 protein, human
  • DNA Helicases
  • Carrier Proteins

Grants and funding

The present study was supported by the National Science Foundation of China (grant no. 82260351).