Overexpression of CENPF is associated with progression and poor prognosis of lung adenocarcinoma

Int J Med Sci. 2021 Jan 1;18(2):494-504. doi: 10.7150/ijms.49041. eCollection 2021.

Abstract

Background and aim: The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. Methods: CENPF expression level was investigated in public online database firstly, the prognosis of CENPF in LUAD were also assessed by Kaplan-Meier analysis. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed using 13 matched pairs of clinical LUAD tissue samples. Subsequently, the impact of CENPF expression on cell proliferation, cell cycle, apoptosis, colony formation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis and colony formation assay, respectively. Finally, experimental xenograft lung cancer model of nude mice armpit of right forelimb to determine the effect of CENPF on LUAD tumorigenesis. Results: CENPF mRNA expression was significantly elevated in LUAD tissues compared with adjacent non-tumor lung tissues in Gene Expression Profiling Interactive Analysis (GEPIA) (P < 0.001). Up-regulated CENPF was remarkably positively associated with pathological stage, relapse free survival (RFS) as well as overall survival (OS) of LUAD patients. Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Conclusion: Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.

Keywords: CENPF; LUAD; cell cycle; prognostic biomarker.

MeSH terms

  • Adenocarcinoma of Lung / diagnosis
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / pathology
  • Animals
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Chromosomal Proteins, Non-Histone / analysis
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Datasets as Topic
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung / pathology
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Mice
  • Microfilament Proteins / analysis
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Chromosomal Proteins, Non-Histone
  • Microfilament Proteins
  • centromere protein F