SKA3, negatively regulated by miR-128-3p, promotes the progression of non-small-cell lung cancer

Per Med. 2022 May;19(3):193-205. doi: 10.2217/pme-2020-0095. Epub 2021 Sep 17.

Abstract

Aim: To investigate the effects of SKA3 on cell proliferation and metastasis in non-small-cell lung cancer (NSCLC) and its underlying mechanism. Methods: Immunohistochemistry was employed to analyze the expression of SKA3 in NSCLC. CCK-8 assay, EdU assay, Transwell assay and flow cytometry analysis were employed to assess cell proliferation, metastatic potential and apoptosis in vitro, respectively. A lung metastasis model was used to evaluate metastasis of NSCLC cells in vivo. A luciferase reporter gene assay was conducted to verify the targeting relationship. Results: SKA3 exhibited high expression in NSCLC tissues and cells. Overexpression of SKA3 remarkably accelerated cell proliferation and metastasis and suppressed apoptosis of NSCLC cells and promoted lung metastasis in a mouse model. miR-128-3p repressed SKA3 expression by targeting it. Conclusion:miR-128-3p inhibited the progression of NSCLC through targeting SKA3.

Keywords: NSCLC; SKA3; apoptosis; invasion; lung metastasis; miR-128-3p; migration; proliferation.

Plain language summary

It is reported that the protein SKA3 can promote the growth and spread of cancer cells in multiple tumors. However, the biological role and action of SKA3 in the progression of non-small-cell lung cancer remain unknown. This study showed that a high level of SKA3 was linked with poor outcomes in non-small-cell lung cancer patients. SKA3 overexpression facilitated cell growth and spread, but inhibited cell death. miR-128-3p directly targeted SKA3 and reversed its effects. Our work suggests that SKA3 and miR-128-3p are promising therapy targets and diagnostic markers for non-small-cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Cell Movement / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism

Substances

  • Cell Cycle Proteins
  • MIRN128 microRNA, human
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Ska3 protein, human