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Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal

Yuxuan Ma1,2, Yuhao Wang1,2, Shu Wang1

  • 1Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127, Changlexi Road, Xi'an, 710032, Shaanxi Province, China.

Clinical and Experimental Medicine
|May 10, 2025
PubMed

Insights

Non-coding RNAs (ncRNAs) regulate programmed cell death (PCD) pathways in gastrointestinal stromal tumors (GIST). Targeting ncRNAs offers new strategies to overcome drug resistance and improve GIST treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the GI tract, often driven by KIT or PDGFRA mutations.
  • Programmed cell death (PCD) pathways, including apoptosis, autophagy, and ferroptosis, are critical in GIST pathogenesis, progression, and response to therapy.
  • Non-coding RNAs (ncRNAs) are increasingly recognized as key regulators of cellular processes, including PCD.

Purpose of the Study:

  • To explore the role of ncRNAs in regulating PCD pathways (apoptosis, autophagy, ferroptosis) in GIST.
  • To investigate how ncRNAs influence GIST proliferation, metastasis, and resistance to tyrosine kinase inhibitors (TKIs).
  • To identify potential therapeutic strategies targeting ncRNA-mediated PCD in GIST.

Main Methods:

  • Review of current literature on ncRNAs, PCD, and GIST.
  • Analysis of molecular interactions between ncRNAs and key signaling pathways (PI3K/AKT, MAPK, mTOR).
  • Examination of ncRNA involvement in TKI resistance mechanisms, including autophagy and ferroptosis.

Main Results:

  • ncRNAs modulate apoptosis, autophagy, and ferroptosis in GIST through interactions with specific molecules (e.g., miR-494, miR-30a, lncRNAs).
  • Suppression of apoptosis is linked to poor GIST prognosis, while autophagy promotes TKI resistance.
  • ncRNAs contribute to secondary resistance to imatinib by affecting autophagic flux and ferroptosis sensitivity.

Conclusions:

  • ncRNAs play a significant role in regulating diverse PCD pathways within GIST.
  • Understanding ncRNA-PCD interactions provides insights into GIST development and drug resistance.
  • Targeting ncRNA-modulated PCD pathways presents a promising therapeutic avenue for enhancing GIST treatment efficacy.
Keywords:
AutophagyFerroptosisGastrointestinal stromal tumorNon-coding RNAProgrammed cell death

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