RUSC1-AS1 promotes the malignant progression of breast cancer depending on the regulation of the miR-326/XRCC5 pathway

Thorac Cancer. 2023 Aug;14(24):2504-2514. doi: 10.1111/1759-7714.15035. Epub 2023 Jul 10.

Abstract

Background: Many long noncoding RNAs (lncRNAs) are the key regulators for cancer progression, including breast cancer (BC). RUSC1 antisense 1 (RUSC1-AS1) has been found to be highly expressed in BC, but its role and potential molecular mechanism in BC remain to be further elucidated.

Methods: Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was utilized to measure RUSC1-AS1, microRNA (miR)-326 and X-ray repair cross-complementing group 5 (XRCC5) expression. Cell proliferation, metastasis, cell cycle, apoptosis and angiogenesis were determined by cell counting kit-8, colony formation, transwell, flow cytometry and tube formation assays. Protein expression was detected by western blot analysis. The targeted relationship between miR-326 and RUSC1-AS1 or XRCC5 was validated using dual-luciferase reporter assay and RIP assay. Xenograft models were constructed to uncover the effect of RUSC1-AS1 on BC tumorigenesis.

Results: RUSC1-AS1 was upregulated in BC, and its downregulation suppressed BC proliferation, metastasis, cell cycle, angiogenesis, and tumor growth. MiR-326 was confirmed to be sponged by RUSC1-AS1, and its inhibitor reversed the regulation of RUSC1-AS1 silencing on BC progression. XRCC5 could be targeted by miR-326. Overexpression of XRCC5 reversed the inhibitory impacts of miR-326 on BC progression.

Conclusion: RUSC1-AS1 could serve as a sponge of miR-326 to promote BC progression by targeting XRCC5, suggesting that RUSC1-AS1 might be a target for BC treatment.

Keywords: RUSC1-AS1; XRCC5; breast cancer; miR-326.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Breast Neoplasms* / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ku Autoantigen / genetics
  • Ku Autoantigen / metabolism
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • XRCC5 protein, human
  • Ku Autoantigen
  • RUSC1 protein, human
  • Adaptor Proteins, Signal Transducing
  • MIRN326 microRNA, human