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Cited by 16Autophagy in Disease and TherapyGlioma Diagnosis and TreatmentCancer, Hypoxia, and Metabolism

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

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Danish, Farheen, Qureshi, Muhammad Asif, Mirza, Talat, Amin, Wajiha, Sufiyan, Sufiyan, Naeem, Sana, Arshad, Fatima, Mughal, Nouman·2024·International Journal of Molecular Sciences
DOI 10.3390/ijms25010572PMC PMC10779014
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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.

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  • PIK3R1 acts as a tumor suppressor by inhibiting the PI3K/AKT signaling pathway, which promotes cell proliferation, migration, and invasion in cancer.

    “Studies have shown that PIK3R1, coding for the protein p85α, acts as a tumor suppressor by inhibiting the PI3K/AKT signaling pathway, which is known for promoting cell proliferation, migration, and invasion in cancer [38].”

    From miR-21 as a diagnostic and prognostic biomarker in glioma: tissue and serum expression analysis in a Pakistani cohort (2026) · cites this paper as [38]

    The Discussion (page unavailable) associates abnormal PI3K/AKT/mTOR activation with tumor development, progression, and invasion, supporting the pathway-related part of the sentence. Our copy does not mention PIK3R1 or p85α, or say that PIK3R1 suppresses tumors by inhibiting that pathway; searches for both terms returned no matching passage. (LLM, conf=0.85)

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Authors
Danish, F., Qureshi, M. A., Mirza, T., Amin, W., Sufiyan, S., Naeem, S., Arshad, F., & Mughal, N.
Affiliations
  • Dow University of Health Sciences (PK)
  • Ziauddin University (PK)
  • Aga Khan University (PK)
Corresponding author
  • Qureshi, Muhammad Asif
  • Mughal, Nouman
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2024-01-01
Volume
25
Issue
1
Pages
572
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms25010572
PMC
PMC10779014
OpenAlex
W4390479317
Cited by
16
References
4
Citations by year
2026: 7 · 2025: 5 · 2024: 4
FWCI
4.85
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eCommons - AKU (Aga Khan University) (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
autophagy, glioma, LC3B, p62, DRAM, autophagy-related genes, high-grade glioma, low-grade glioma, tumor hypoxia, chemoresistance, Vps34, Beclin-1, ULK2, UVRAG, mTOR, PI3K/Akt signaling, tumor progression
MeSH terms
Beclin-1, Sequestosome-1 Protein, Hypoxia, Autophagy, Genes, Regulator, Glioma, Humans

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