SLC7A1, SGK1 and HMGB2 are overexpressed in cervical cancer tissues and the miR‑23b‑3p/HMGB2 axis regulates cell migration and invasion

Mol Med Rep. 2025 Sep;32(3):235. doi: 10.3892/mmr.2025.13600. Epub 2025 Jun 27.

Abstract

MicroRNA (miRNA/miR)‑124‑3p and miR‑23b‑3p are tumor suppressor miRNAs that are associated with advanced cervical cancer (CC), regulating proliferation, migration, invasion, apoptosis and metastasis; however, the identity and function of the various genes regulated by these miRNAs remain unknown. The present study predicted the specific and shared targets of miR‑124‑3p and miR‑23b‑3p, cellular processes and signaling pathways involving the predicted targets. SLC7A1 was found among the shared targets, SGK1 among the targets of miR‑124‑3p and HMGB2 as a target of miR‑23b‑3p. SLC7A1, SGK1 and HMGB2 mRNA expression was markedly increased in patients with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and levels of SGK1 and HMGB2 were associated with CC progression. SLC7A1, SGK1 and HMGB2 interact with proteins involved in cellular processes associated with cancer progression. Overexpression of miR‑124‑3p decreased mRNA of SLC7A1 in C‑33A cells, and of SGK1 in both cell lines. Ectopic expression of miR‑23b‑3p decreased HMGB2 levels in C‑33A and CaSki, and reduced cell migration and invasion. HMGB2 knockdown experiments revealed that HMGB2 modulates migration and invasion of CC cell lines. In conclusion, the results of the present study suggest that miR‑124‑3p and miR‑23b‑3p modulate processes associated with carcinogenesis and tumor progression through their individual and shared target mRNAs and that the miR‑23b‑3p/HMGB2 axis is among the mechanisms that modulate migration and invasion in CC.

Keywords: SGK1 and HMGB2; SLC7A1; cervical cancer; invasion; miR‑124‑3p; miR‑23b‑3p; migration; progression.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HMGB2 Protein* / genetics
  • HMGB2 Protein* / metabolism
  • Humans
  • Immediate-Early Proteins* / genetics
  • Immediate-Early Proteins* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / metabolism
  • Serum-Glucocorticoid Regulated Kinases
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology

Substances

  • MicroRNAs
  • Protein Serine-Threonine Kinases
  • Immediate-Early Proteins
  • HMGB2 Protein
  • Serum-Glucocorticoid Regulated Kinases