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PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Studies report that some tumor cells evade therapeutic stress by entering a dormant, drug-tolerant state known as "persistence."
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In these persistent cells, glucose metabolism is downregulated, leading to decreased glutathione (GSH) levels and increased sensitivity to GPX4 inhibitors such as RSL3.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
RSL3 has demonstrated efficacy against persistent tumor cells in vitro and in vivo.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Moreover, inhibitors of YAP, such as verteporfin (VP) and CA3, can further enhance ferroptosis-induced cytotoxicity.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The combination of RSL3 with IM has shown synergistic therapeutic effects in GIST .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Sun et al. found that IM treatment increases intracellular Fe levels and lipid ROS while depleting GSH.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The ferroptosis inhibitor Ferrostatin-1 can partially block these effects.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Additionally, STUB1 knockdown or GPX4 overexpression reverses IM-induced ferroptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
STUB1 was identified as a novel E3 ubiquitin ligase that promotes GPX4 ubiquitination and degradation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Combined treatment with RSL3 and IM significantly enhances ferroptosis and suppresses GIST proliferation both in vitro and in vivo .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The ferroptotic process and its key molecular events in GIST cells are illustrated in Fig. 5.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Iron accumulation leads to lipid peroxidation and oxidative stress, culminating in ferroptotic cell death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Disruption of iron metabolism is closely linked to this process in GIST.Fig.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
5Mechanisms and clinical potential of ferroptosis in GIST treatment (Created by BioRender) Mechanisms and clinical potential of ferroptosis in GIST treatment (Created by BioRender) In addition to its therapeutic potential, ferroptosis is associated with GIST prognosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Zhuang et al. reported that transferrin receptor (TFRC) expression is significantly upregulated in high-risk GIST patients, as defined by NIH risk criteria.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
High TFRC expression correlates with increased recurrence risk.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Delvaux et al. further validated TFRC as a prognostic biomarker.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Tissue microarray (TMA) analysis demonstrated that elevated TFRC levels were associated with increased mitotic activity, greater tumor aggressiveness, and enhanced YAP expression/activation in human GIST specimens .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Ferroptosis and apoptosis are two distinct forms of PCD, each governed by different mechanisms but closely interconnected.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Ferroptosis is defined by iron accumulation and lipid peroxidation, while apoptosis involves DNA fragmentation, mitochondrial dysfunction, and caspase activation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Recent studies suggest that although these pathways can operate independently, ferroptosis may influence the initiation and progression of apoptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
For instance, GPX4, a key ferroptosis inhibitor, prevents lipid peroxidation and maintains cell viability.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Conversely, iron accumulation can trigger mitochondrial dysfunction through Fenton reactions, leading to a loss of mitochondrial membrane potential and activation of apoptotic cascades .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Inactivation of GPX4 promotes lipid peroxidation and activates apoptotic markers like caspase-3, further amplifying cell death .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Excessive ROS accumulation, a hallmark of ferroptosis, can activate signaling pathways such as p53, JNK, and MAPK, contributing to apoptosis induction .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These interactions highlight a regulatory overlap between ferroptosis and apoptosis, offering new therapeutic insights.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Figure 6 illustrates the dynamic crosstalk between ferroptosis, apoptosis, and autophagy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Fig. 6Interaction mechanisms between ferroptosis, apoptosis, and autophagy (Created by BioRender) Interaction mechanisms between ferroptosis, apoptosis, and autophagy (Created by BioRender) Ferroptosis also exhibits complex interactions with autophagy, a lysosome-dependent degradation process that removes damaged proteins, organelles, and iron, maintaining cellular homeostasis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Depending on the context, autophagy may either suppress or promote ferroptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In some cases, autophagy clears excess iron, reducing Fenton reactions and preventing lipid peroxidation .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In contrast, excessive autophagy may degrade antioxidant proteins like GPX4, sensitizing cells to ferroptosis .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Ferroptosis can also modulate autophagy-related pathways by influencing key regulators such as mTOR and Beclin1, thereby affecting cell survival .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
ROS generated during ferroptosis can also activate autophagy through ATG proteins, forming a feedback loop that intensifies oxidative damage .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
This bidirectional regulation allows cells to fine-tune their response to stress and determine survival or death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The crosstalk among ferroptosis, apoptosis, and autophagy reflects a dynamic, multilayered system of cell fate regulation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These interactions are context-dependent and vary across physiological and pathological conditions.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In some cancers, ferroptosis regulates cell viability by interacting with apoptosis and autophagy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
For example, ferroptosis-induced mitochondrial dysfunction can reduce ATP levels and activate autophagy, while autophagy, in turn, can alleviate ferroptosis by removing damaged mitochondria and iron .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Furthermore, ferroptosis is linked to cell cycle regulation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
It can influence key regulators such as p53 and cyclin D through apoptotic interactions, thereby affecting proliferation and cell death .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In certain tumor models, ferroptosis modulates chemotherapy resistance through its relationship with autophagy, offering new therapeutic opportunities .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The interaction between apoptosis and ferroptosis underscores the critical role of mitochondria in drug resistance and cell death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Collectively, the interplay between ferroptosis, apoptosis, and autophagy provides a comprehensive framework for understanding tumor cell fate and offers novel targets for precision oncology.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Cell death is a complex biological phenomenon crucial in physiological and pathological processes involving apoptosis, necrosis, and autophagy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These processes are vital for maintaining homeostasis and contribute significantly to the onset and progression of various diseases.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In recent years, ncRNAs have emerged as key regulatory factors in cell death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
ncRNAs are RNA molecules that do not encode proteins but influence gene expression and cellular functions through multiple mechanisms.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
The main types of ncRNAs—miRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—regulate cell death via distinct pathways.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
MiRNAs bind to target mRNAs to inhibit translation or promote mRNA degradation, affecting gene expression in cell death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
LncRNAs regulate gene transcription, post-transcriptional modifications, and translation by interacting with DNA, RNA, or proteins, thus influencing cell survival or death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
CircRNAs act as molecular "sponges" that sequester miRNAs or other molecules, modulating their functions and impacting the progression of cell death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Figures 7 and 8 illustrate the regulatory roles of these ncRNAs in cell death pathways, encompassing the actions of different types of ncRNAs.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Furthermore, ncRNAs are involved in several aspects of GIST biology.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Table 3 lists key ncRNA types, including miRNAs, lncRNAs, and circRNAs, along with their targets and functions.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
By regulating processes such as cell proliferation, migration, and apoptosis, these ncRNAs play critical roles in the initiation and progression of GIST.Fig.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
7Network diagram of different ncRNAs regulating cell death pathwaysFig.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
8Interaction mechanisms between cell death pathwaysTable 3Roles of Non-coding RNAs in GIST and their targets and functionsncRNA TypeTargetFunctionRole in GISTmiRNASOX9Regulates cell proliferation, differentiation, migration, and apoptosisSOX9 is an important oncogene in GIST, and miR-34a inhibits its expression, reducing tumor cell proliferationBcl-2Inhibits Bcl-2 family proteins, promoting apoptosismiR-144 regulates Bcl-2 expression, enhancing apoptosis in GIST cellsVEGFInvolved in angiogenesis and tumor neovascularizationmiR-214 targets VEGF to suppress angiogenesis in GIST cellslncRNAH19Regulates the activity of transcription factors, involved in the regulation of cell proliferation and apoptosisH19 acts as an oncogene in GIST, promoting cell proliferation and anti-apoptotic effectsMALAT1Affects cell migration, proliferation, and metastasis, involved in cell cycle regulationHigh expression of MALAT1 in GIST is associated with tumor cell invasiveness and metastatic potentialPVT1Interacts with c-Myc to promote tumor cell proliferation and anti-apoptosisOverexpression of PVT1 in GIST enhances tumor growth and resistance to therapycircRNAciRS-7Competes with miRNAs to inhibit their function, regulating tumor-associated gene expressionciRS-7 regulates miR-7 in GIST, influencing cell proliferation and apoptosiscirc-0001438Modulates miR-130a-3p to affect tumor invasivenesscirc-0001438 promotes GIST progression by enhancing the function of miR-130a-3ppiRNAPIWIL1Participates in the regulation of gene transcription, affecting cell proliferation and apoptosisOverexpression of PIWIL1 is closely associated with GIST cell proliferation and migration Network diagram of different ncRNAs regulating cell death pathways Interaction mechanisms between cell death pathways Roles of Non-coding RNAs in GIST and their targets and functions ncRNAs, including microRNAs (miRNAs), lncRNAs, and circRNAs, are crucial regulators of gene expression and have been increasingly recognized for their roles in apoptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In various tumors, including GIST, ncRNAs modulate apoptosis by targeting key genes and signaling pathways, thereby influencing tumor progression and therapeutic response.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
miRNAs regulate apoptosis by binding to target genes and modulating the expression of apoptosis-related proteins.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In GIST, several miRNAs have been linked to drug sensitivity and cell death regulation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
For instance, miR-21 promotes anti-apoptotic activity by downregulating tumor suppressors such as PDCD4 and PTEN .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In contrast, miR-34a acts as a tumor suppressor by enhancing p53 signaling and downregulating Bcl-2 family proteins, activating the mitochondrial apoptotic pathway and inhibiting tumor growth .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Similarly, miR-155 enhances apoptosis by suppressing Bcl-2 expression and shows therapeutic potential .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In ovarian granulosa cells, miR-484 targets the LINC00958/SESN2 axis to modulate mitochondrial function and promote apoptosis under oxidative stress, offering the potential for translational application .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
lncRNAs exhibit complex regulatory functions and play important roles in modulating apoptosis in GIST.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
HOTAIR, a widely studied oncogenic lncRNA, inhibits apoptosis by repressing p21 and p53 via EZH2 binding, contributing to GIST proliferation and drug resistance .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
MALAT1 suppresses autophagy and enhances GIST cell survival , while GAS5 activates the p53 pathway to promote apoptosis and inhibit proliferation and migration .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
LINC00958 competes with miR-484 to regulate SESN2 expression, influencing mitochondrial function and apoptotic signaling .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Furthermore, lncRNA HIF1A-AS2 promotes IM resistance under hypoxic conditions by inhibiting apoptosis and enhancing autophagy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Silencing HIF1A-AS2 restores IM sensitivity and increases apoptosis in GIST cells .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These findings suggest that lncRNAs are promising therapeutic targets for modulating apoptosis and overcoming drug resistance in GIST.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
circRNAs are structurally stable ncRNAs that play emerging roles in apoptosis regulation.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Unlike linear RNAs, circRNAs resist degradation and often function as miRNA sponges to modulate downstream gene expression.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In non-small cell lung cancer (NSCLC), circRNA-CPA4 binds competitively to miR-1183, thereby upregulating PDPK1 and promoting proliferation while inhibiting apoptosis .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In GIST, circRNA CIRS-7 sequesters miR-7, relieving inhibition on Bcl-2 family members and suppressing apoptosis .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In gastric cancer, circRNA ciRS-7 modulates miR-7 and miR-671 to enhance apoptosis and improve chemotherapy sensitivity .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
These findings highlight circRNAs as novel regulators of apoptosis and potential targets in cancer therapy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Recent studies have highlighted the critical role of ncRNAs in regulating autophagy.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
ncRNAs modulate autophagy by directly targeting autophagy-related genes and interacting with key signaling pathways that control tumor cell survival and death.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In GIST, abnormal expression of ncRNAs has been closely linked to tumorigenesis, progression, and drug resistance.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Among them, miRNAs and lncRNAs are the most extensively studied, offering new therapeutic targets for GIST.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
miRNAs regulate autophagy primarily by targeting autophagy-related genes such as ATGs, LC3, and Beclin1.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Autophagy is commonly initiated by signaling pathways, including mTOR and PI3K/Akt, which are frequent miRNA targets .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
For instance, the miR-30 family suppresses autophagy by directly targeting mTOR and ATG7 , while miR-101 enhances autophagy through mTOR inhibition, thereby reducing tumor cell proliferation .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In GIST, miRNAs may influence autophagy to regulate drug resistance and tumor growth.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
miR-126 modulates the PI3K/Akt pathway and thereby alters autophagy activity , whereas miR-183 suppresses Beclin1, inhibiting autophagy and promoting GIST cell proliferation .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Additionally, circRNA circ-CCS is significantly elevated in the serum of IM-resistant GIST patients.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Its silencing inhibits proliferation and autophagy while promoting apoptosis.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Mechanistic studies revealed that circ-CCS targets miR-197-3p to downregulate ATG10 expression, suggesting a role in autophagy-mediated drug resistance .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
lncRNAs regulate autophagy by interacting with transcription factors, miRNAs, and autophagy-related proteins.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In GIST, altered expression of specific lncRNAs has been linked to autophagy activity and tumor behavior changes.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
HOTAIR enhances autophagy by modulating the PI3K/Akt/mTOR axis, contributing to tumor proliferation and reduced drug sensitivity .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
MALAT1, another well-studied lncRNA, binds to autophagy suppressors to inhibit autophagy and promote cell survival and invasion .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
lncRNA ATB has also been shown to activate autophagy-related proteins, thereby promoting tumor growth and resistance .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
Autophagy is a protective mechanism under therapeutic stress by removing damaged components and maintaining cellular viability.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
However, excessive autophagy may lead to treatment resistance.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
ncRNAs regulate autophagy in this context and influence drug sensitivity.
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
For example, miR-138 suppresses autophagy by targeting ATG5, enhancing chemosensitivity .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
In contrast, lncRNA NEAT1 promotes resistance by increasing autophagy in GIST cells under targeted therapy .
PMC12065685
Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors
CircRNAs also play a role; circRNA CDR1as functions as a miRNA sponge to regulate ATG7 expression, modulating autophagy activity and drug response in GIST .