Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines

Xiao-Rong Yang1, Yan Xiong2, Hong Duan3

  • 1Department of Operation Room, West China Hospital, Sichuan University, No 37, Guo Xue Lane, Chengdu, Sichuan, 610041, People's Republic of China. jafsdfdfs@163.com.

Abstract

Insights

Methotrexate resistance in osteosarcoma is linked to altered gene expression. Key genes in aminoacyl-tRNA biosynthesis and cell cycle pathways may drive this resistance, offering potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Osteosarcoma is a primary bone cancer with significant treatment challenges.
  • Methotrexate (MTX) is a chemotherapy agent used in osteosarcoma treatment.
  • Understanding MTX resistance mechanisms is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the molecular mechanisms of methotrexate (MTX) resistance in osteosarcoma.
  • To identify differentially expressed genes (DEGs) associated with MTX resistance.
  • To explore the functional roles of these DEGs in osteosarcoma progression.

Main Methods:

  • Microarray data (GSE16089) from MTX-sensitive and resistant osteosarcoma cells were analyzed.
  • Differentially expressed genes (DEGs) were identified and functionally annotated using GO and KEGG databases.
  • Transcription factors (TFs), tumor-associated genes (TAGs), and protein-protein interaction (PPI) networks were constructed.

Main Results:

  • 690 up-regulated and 626 down-regulated genes were identified.
  • Up-regulated genes were linked to transfer RNA (tRNA) aminoacylation (e.g., AARS, PARS2).
  • Down-regulated genes were associated with the mitotic cell cycle (e.g., AURKA, CCNB1, CDK1, CENPA).

Conclusions:

  • Genes such as AARS, AURKA, AURKB, CENPA, CCNB1, CCNE2, and CDK1 may contribute to MTX resistance.
  • These genes are implicated in aminoacyl-tRNA biosynthesis, cell cycle regulation, and p53 signaling pathways.
  • Identifying these genes provides insights into potential therapeutic strategies for overcoming MTX resistance in osteosarcoma.