Investigating the Association between the Autophagy Markers LC3B, SQSTM1/p62, and DRAM and Autophagy-Related Genes in Glioma

Farheen Danish, Muhammad Asif Qureshi, Talat Mirza, Wajiha Amin, Sufiyan Sufiyan, Sana Naeem, Fatima Arshad, Nouman Mughal

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers’ expression in low-grade gliomas (LGGs) and high-grade gliomas (HGGs). In 39 glioma cases, we assessed the protein expression of autophagy markers LC3B, SQSTM1/p62, and DRAM by immunohistochemistry (IHC) and the mRNA expression of the autophagy genes PTEN, PI3K, AKT, mTOR, ULK1, ULK2, UVRAG, Beclin 1, and VPS34 using RT-qPCR. LC3B, SQSTM1/p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases, respectively. The expression of LC3B and SQSTM1/p62 was notably higher in HGGs compared to LGGs. VPS34 exhibited a significant differential expression, displaying increased fold change in HGGs compared to LGGs. Additionally, it exhibited robust positive associations with Beclin1 (rs = 0.768), UVRAG (rs = 0.802), and ULK2 (rs = 0.786) in HGGs. This underscores a potential association between autophagy and the progression of gliomas. We provide preliminary data for the functional analysis of autophagy using a cell culture model and to identify potential targets for therapeutic interventions.

Original languageEnglish (US)
Article number572
JournalInternational Journal of Molecular Sciences
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 2024

Keywords

  • DRAM
  • LC3B
  • SQSTM1/p62
  • autophagy
  • autophagy-related genes (ATGs)
  • high-grade gliomas (HGGs)
  • low-grade gliomas (LGGs)

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