KLC3 activates PI3K/AKT signaling and promotes ovarian cancer cell proliferation and migration through COL3A1

Oncol Rep. 2025 Jun;53(6):67. doi: 10.3892/or.2025.8900. Epub 2025 Apr 17.

Abstract

Ovarian cancer (OC) is a prevalent malignancy; however, the role of kinesin light chain 3 (KLC3) in OC remains unclear. The present study conducted a comprehensive investigation of KLC3 using bioinformatics analysis, as well as in vitro and in vivo experiments. The findings revealed that KLC3 expression was significantly upregulated in the OC group compared with that in the normal group, and high KLC3 expression in patients with OC was associated with a poorer overall survival. Functional studies demonstrated that targeting KLC3 effectively suppressed the proliferation, migration, epithelial‑mesenchymal transition and DNA damage resistance of OC cells in vitro, while also inhibiting tumor growth in vivo, underscoring the pivotal role of KLC3 in tumor progression and metastasis. Additionally, RNA‑sequencing analysis identified collagen type III α1 (COL3A1) as a potential downstream gene cooperating with KLC3 to promote the occurrence and development of OC through the PI3K/AKT signaling pathway. Rescue experiments revealed that the KLC3 knockdown‑induced suppression of the malignant phenotype could be partially reversed by overexpression of COL3A1. In summary, the present findings demonstrated that KLC3 acts as an oncogene by influencing COL3A1 expression to promote the proliferation and migration of OC cells in vivo and in vitro.

Keywords: PI3K/AKT signaling pathway; collagen type III α1; kinesin light chain 3; ovarian cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Collagen Type III* / genetics
  • Collagen Type III* / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kinesins
  • Mice
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism
  • Middle Aged
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / mortality
  • Ovarian Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinases* / genetics
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Microtubule-Associated Proteins
  • COL3A1 protein, human
  • Collagen Type III
  • Klc3 protein, mouse
  • Kinesins