Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Investigating the Association between Autophagy Markers LC3B, P62, DRAM and Autophagy-Related Genes in Glioma

Farheen Danish
,
Muhammad Asif Qureshi
* ORCID logo ,
Talat Mirza
,
Wajiha Amin
,
Sufiyan Sufiyan
,
Sana Naeem
,
Fatima Arshad
,
Nouman Mughal
*
Version 1 : Received: 27 December 2023 / Approved: 28 December 2023 / Online: 28 December 2023 (09:59:29 CET)

A peer-reviewed article of this Preprint also exists.

Danish, F.; Qureshi, M.A.; Mirza, T.; Amin, W.; Sufiyan, S.; Naeem, S.; Arshad, F.; Mughal, N. Investigating the Association between the Autophagy Markers LC3B, SQSTM1/p62, and DRAM and Autophagy-Related Genes in Glioma. Int. J. Mol. Sci. 2024, 25, 572. Danish, F.; Qureshi, M.A.; Mirza, T.; Amin, W.; Sufiyan, S.; Naeem, S.; Arshad, F.; Mughal, N. Investigating the Association between the Autophagy Markers LC3B, SQSTM1/p62, and DRAM and Autophagy-Related Genes in Glioma. Int. J. Mol. Sci. 2024, 25, 572.

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 (LGG) and high-grade gliomas (HGG). In 39 glioma cases, we assessed protein expression of autophagy markers LC3B, p62, and DRAM by immunohistochemistry (IHC) and mRNA expression of autophagy genes; PI3K, AKT, m-TOR, PTEN, ULK1, ULK2, UVRAG, Beclin 1 and VPS34 using RT-qPCR. Livak’s method was used to analyze the relative changes in gene expression and multi-variate Anova test and Spearman's correlation tests were performed for statistical significance. LC3B, p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases respectively. The expression of LC3B and p62 was notably higher in HGG compared to LGG. VPS34 exhibited a significant differential expression and increased fold change and demonstrated strong positive correlations with Beclin1 (rs=0.768), UVRAG (rs=0.802), and ULK2 (rs=0.786) in HGG compared to LGG, thus highlighting the potential link between autophagy and glioma progression. We Provide preliminary data for functional analysis of autophagy using cell culture model and to identify potential targets for therapeutic interventions

Keywords

Autophagy; Autophagy related genes (ARG); High grade gliomas (HGG), Low grade gliomas (LGG), LC3B, p62 & DRAM

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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