N7-methyladenosine-induced SLC7A7 serves as a prognostic biomarker in pan-cancer and promotes CRC progression in colorectal cancer

Sci Rep. 2024 Dec 28;14(1):30755. doi: 10.1038/s41598-024-80885-2.

Abstract

Solute transport family 7A member 7 (SLC7A7) mutations contribute to lysinuric protein intolerance (LPI), which is the mechanism of action that has been extensively studied. In colorectal cancer (CRC), SLC7A7 appears to play a role, but the features and mechanisms are not yet well understood. Survival was analyzed using the Kaplan-Meier analysis. Enrichment analysis was performed to characterize, immune infiltration, methylation, genetic instability, and crucial pathways of SLC7A7. Afterward, functional experiments were conducted in vitro to investigate how SLC7A7 affects tumor metastasis. Mechanistically, quantitative real-time PCR (qRT-PCR), western blot (WB), and methylated RNA immunoprecipitation (me-RIP) were carried out to confirm the methylation modification of SLC7A7 and related functions. High levels of expression of SLC7A7 are predictive of a worse prognosis for CRC patients. Enrichment analysis showed that SLC7A7 was significantly enriched during EMT and could be enriched in the Wnt/β-catenin signaling pathway, immune infiltration analysis of pan-cancer showed that SLC7A7 was significantly enriched in macrophages, and methylation analysis showed that SLC7A7 methylation modification affected the prognosis of specific cancers. SLC7A7 was indicated to promote the migration and invasion of CRC cells in in vitro functional experiments. Mechanistically, SLC7A7 was observed to potentially interact with the Wnt/β-catenin signaling pathway, possibly by influencing adenomatous polyposis coli (APC) expression. Furthermore, we identified that SLC7A7 undergoes N7-methylguanosine (m7G) modification, which may regulate SLC7A7 mRNA stability, with Quaking (QKI) potentially playing a role in this process by recognizing the m7G modification. Our results indicate that SLC7A7 may promote CRC metastasis through the SLC7A7/APC/Wnt/β-catenin signaling pathway. Moreover, m7G modification might be involved in regulating SLC7A7 mRNA stability, highlighting a novel layer of regulation.

Keywords: Colorectal cancer; Invasion; Migration; SLC7A7; m7g modification.

MeSH terms

  • Adenosine* / analogs & derivatives
  • Adenosine* / metabolism
  • Amino Acid Transport System y+L
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • DNA Methylation
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Prognosis
  • Wnt Signaling Pathway

Substances

  • Biomarkers, Tumor
  • Adenosine
  • SLC7A7 protein, human
  • N-methyladenosine
  • Amino Acid Transport System y+L