PMCID string | Title string | Sentences string |
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PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | This process ultimately supports tumor cell survival and proliferation while inhibiting apoptosis Tumor Metabolism and Apoptosis Inhibition Mechanisms Driven by SDH Deficiency (Created by BioRender). |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | This figure illustrates the key molecular mechanisms underlying GIST associated with SDH deficiency, observed in approximately 15% of GIST cases. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The accumulation of succinate and fumarate affects the PHD and HIF signaling pathways, subsequently activating the MAPK pathway. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | This process ultimately supports tumor cell survival and proliferation while inhibiting apoptosis In addition, GIST exhibits high levels of ETV1 expression, a transcription factor downstream of the MEK-MAPK pathway. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | ETV1 is essential for ICC development and its transformation into GIST cells, driving abnormal proliferation and inhibiting apoptosis . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The activation of KIT synergizes with ETV1, further promoting aberrant cell proliferation and apoptosis suppression . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Other genetic alterations, such as SDH gene silencing and mutations in RAS, BRAF, NF1, and FGFR1, have also been identified in a minority of GIST cases . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | These genetic changes present potential targets for individualized therapy. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | With the advancement of targeted therapy, systemic treatment of GIST has significantly progressed, primarily focusing on tyrosine kinase inhibitors (TKIs) targeting KIT and PDGFRA mutations. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | However, GIST exhibits considerable molecular heterogeneity. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Approximately 5–10% of patients have succinate dehydrogenase (SDH)-deficient GISTs , which are more frequently seen in younger individuals and often associated with hereditary syndromes. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | SDH deficiency leads to succinate accumulation and activation of oncogenic signaling pathways . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | This subtype responds poorly to conventional TKIs and displays distinct molecular features such as high expression of neural markers, FGFR signaling activation, and epithelial-mesenchymal transition (EMT), indicating the need for alternative therapeutic approaches . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | In PDGFRA-mutant GISTs, the D842V mutation (exon 18), which accounts for approximately 5% of cases, confers primary resistance to imatinib and sunitinib. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The novel TKI avapritinib has demonstrated promising efficacy in this mutation subtype and represents a new direction for precision therapy . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Moreover, the efficacy of immune checkpoint inhibitors (ICIs) in GIST remains uncertain. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Studies have shown that SDH-deficient GISTs possess an immune-cold microenvironment, which may influence their response to ICIs . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | In addition, immune-related adverse events (irAEs), such as hearing loss, have been reported during ICI treatment and warrant attention . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The neutrophil-to-eosinophil ratio (NER) has recently been proposed as a potential prognostic biomarker. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Although its role in GIST is not well-established, it may offer insights for future personalized treatment strategies . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | KIT and PDGFRA have been identified in treating GIST as type III receptor tyrosine kinases, leading to TKIs such as imatinib (IM). |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | As a targeted therapy, IM has become one of the standard treatments for GIST. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | It inhibits tumor growth by suppressing the tyrosine kinase activity of KIT and PDGFRA . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Over the past two decades, IM has significantly improved the median survival of patients, extending it from 18 months to over 5 years . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Although IM remains the first-line therapy for GIST, disease progression typically occurs after a median duration of 20–24 months . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The most studied mechanism of IM resistance involves secondary mutations in KIT or PDGFRA and the activation of alternative pathways such as MEK-MAPK and PI3K-AKT. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | This phenomenon, known as secondary resistance, limits the effectiveness of IM . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | These mutations primarily occur in the ATP-binding domain (exon 13 or 14 of KIT; exon 14 of PDGFRA) or the activation loop (exon 17 of KIT; exon 18 of PDGFRA) [27–30]. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Sunitinib and regorafenib are currently used as standard second and third-line therapies for IM-resistant GIST . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | However, treating secondary resistance remains challenging, as the molecular mechanisms underlying resistance to these drugs are not fully understood. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Studies suggest that IM can induce autophagy, possibly contributing to developing secondary resistance . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Additionally, IM has been shown to induce ferroptosis and apoptosis [35–40], highlighting programmed cell death (PCD) as a promising therapeutic target for GIST. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Table 1 summarizes the major drugs currently used for GIST treatment, their targets and mechanisms of action. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Table 1Key drugs, their targets, and signaling pathways in the treatment of GISTDrug NameTargetSignaling pathwayRole in GIST treatmentImatinibc-Kit, PDGFRInhibits the activation of c-Kit and PDGFR, blocking tumor cell proliferation and survival signaling pathwaysEffective in the treatment of GIST, especially in patient... |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | In GIST, apoptosis, autophagy, and ferroptosis are the primary forms of cell death. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Table 2 summarizes the key regulatory factors involved in these pathways and their functional impacts on GIST cells. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The apoptotic pathway is regulated by p53 and the Bcl-2 family, while autophagy involves Beclin-1, LC3, and the mTOR pathway. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Ferroptosis is controlled by glutathione peroxidase 4 (GPX4), ferroportin, and the Fenton reaction. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Studies have shown that suppression of apoptosis correlates with poor prognosis in GIST patients, whereas the role of autophagy can vary under different conditions [33, 44–46].Table 2Molecular regulators of cell death mechanisms in GISTCell Death TypeRegulatorMechanism of ActionRole in GISTApoptosisp53p53 upregulates p... |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | During GIST progression, ferroptosis appears to function similarly to apoptosis, with ferroptosis-related proteins identified as potential targets and predictive markers for TKI therapy [35–37]. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | As a novel therapeutic target, developing ferroptosis-specific drugs is promising for treating advanced GIST . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Apoptosis, one of the most extensively studied forms of PCD, is characterized by cellular shrinkage, an undulated yet intact plasma membrane, nuclear condensation, and fragmentation, indicative of its non-inflammatory nature. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Apoptotic cells exhibit characteristic morphological changes, including the formation of apoptosomes, which consist of apoptotic peptidase activating factor 1 (APAF1) and caspase-9 . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The apoptosis pathway is classified into intrinsic and extrinsic pathways and further divided into the mitochondrial pathway , death receptor pathway , and endoplasmic reticulum (ER) stress pathway . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The intrinsic (mitochondrial) and extrinsic pathways are the most extensively studied. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The extrinsic pathway is typically triggered by activating tumor necrosis factor (TNF) receptor family members . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The intrinsic pathway is initiated by increased mitochondrial outer membrane permeability (MOMP) and cytochrome c release, leading to apoptosome formation . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The Bcl-2 family plays a critical regulatory role in this pathway and is divided into three subfamilies: pro-apoptotic BH3-only proteins (e.g., Bim, Bid, Puma), anti-apoptotic Bcl-2 family members (e.g., Bcl-2, Mcl-1), and effector molecules (e.g., Bax, Bak) . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | In contrast, the extrinsic pathway is initiated by activating pro-apoptotic death receptors, which are cell membrane proteins, including Fas and TNFR. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Death receptors are activated by binding specific ligands, leading to the recruitment of adaptor proteins such as FADD via their death domains (DD) [58–60]. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Evasion of apoptosis and the aberrant expression of survival proteins are among the most common alterations during malignant transformation. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | By avoiding apoptosis, malignant cells enhance their survival and develop drug resistance [61–63]. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | As understanding of apoptotic mechanisms has advanced, a limited number of FDA-approved anticancer drugs have been developed to directly target apoptosis pathways. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Additionally, many FDA-approved anticancer drugs targeting cell survival and proliferation pathways exert their anti-tumor effects by modulating apoptotic signaling pathways . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | This review examines the molecular functions of PCD pathways in GIST, focusing on their roles in the pathogenesis, malignancy, and responses to TKI therapies. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Additionally, we emphasize the significance of non-coding RNAs (ncRNAs) in these pathways, as growing evidence suggests that ncRNAs play critical roles across various pathways. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Investigating the interplay between these pathways and ncRNAs may offer new research directions and therapeutic strategies for GIST. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Apoptosis plays a key role in the pathogenesis and biology of GIST), particularly in changes in apoptotic signaling and drug resistance following TKI therapy, such as IM. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The most common driver mutations in GIST involve the KIT and PDGFRA genes, which activate multiple downstream signaling pathways that regulate cell survival and apoptosis. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Overexpression of the transcription factor ETV1 may facilitate the transformation of interstitial cells of Cajal into GIST cells while suppressing apoptosis, contributing to tumor progression. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Activating mutations in the c-KIT gene result in constitutive KIT tyrosine kinase activity, which provides continuous proliferative and survival signals—one of the central mechanisms in GIST pathogenesis. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | While inhibition of apoptosis and dysregulation of the cell cycle are likely early molecular events in GIST, the precise mechanisms remain under investigation. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Driver mutations in KIT and PDGFRA activate multiple pathways that disrupt the expression and function of apoptotic regulators. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Constitutively active KIT signaling enables tumor cells to evade apoptosis. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Cyclin D1 is significantly overexpressed in KIT-independent GIST and is associated with antiproliferative and pro-apoptotic responses, indicating a role for cell cycle regulators in the transition from KIT dependence to resistance . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Alterations in E2F1, p53, p16, and p27KIP1 are more frequent in malignant GIST, further implicating apoptosis escape in tumor progression . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Bcl-2, a classic anti-apoptotic protein, is highly expressed in GIST and correlates with poor prognosis. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Cunningham et al. reported shorter survival in patients with high Bcl-2 expression, supporting its role in apoptosis evasion . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | APAF-1, a core component of the apoptosome, is negatively regulated by KIT expression, suppressing apoptosis in GIST . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | FAM96A, a tumor suppressor that enhances mitochondria-mediated apoptosis via interaction with APAF1, is significantly downregulated in GIST, suggesting a loss of pro-apoptotic function . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | FOXO transcription factors, particularly FOXO3a, promote apoptosis by upregulating BIM . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Apoptosis evasion supports GIST growth and survival and contributes to resistance. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Although IM has strong antiproliferative effects, it fails to induce sufficient apoptosis, pushing cells into a quiescent state, a potential source of resistance . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Upregulation of p27(Kip1) and loss of Cyclin A through the APC/CDH1-SKP2-p27(Kip1) axis facilitates apoptosis evasion and quiescence . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Apoptosis-related proteins are valuable biomarkers for predicting GIST behavior and prognosis. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Wang et al. demonstrated a correlation between telomerase activity, apoptotic intensity, and GIST malignancy, noting that apoptosis progressively declines in benign and potentially malignant GIST . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Risk stratification based on the Ki-67 index, tumor size, and location helps predict recurrence in IM-naive patients . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Nemoto et al. found that high-risk GIST cases exhibit elevated labeling indices (LIs) for Ki-67, ssDNA, Cyclin A, and CDK2, Survivin (BIRC5), an anti-apoptotic protein, inhibits the extrinsic pathway via interaction with XIAP . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Its expression is elevated in GIST and downregulated following KIT inhibition, implying a role in KIT-mediated survival signaling . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | FOXO proteins activate apoptosis through multiple mechanisms, including the induction of Bcl-2 pro-apoptotic members, expression of death ligands (e.g., FasL), and upregulation of CDK inhibitors (Fig. 2). |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | FOXO1 influences GIST proliferation, apoptosis, and cell cycle through phosphorylation-dependent mechanisms .Fig. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | 2Fas-Mitochondria-Dependent Apoptosis Pathway (Created by BioRender). |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | This figure depicts how the extrinsic apoptosis pathway mediated by the death receptor Fas intersects with the mitochondrial pathway. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Mitochondrial release of cytochrome C forms apoptosomes, activating caspase family enzymes (such as Caspase-9, Caspase-3/6/7), which leads to apoptosis. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | However, survival inhibits this process Fas-Mitochondria-Dependent Apoptosis Pathway (Created by BioRender). |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | This figure depicts how the extrinsic apoptosis pathway mediated by the death receptor Fas intersects with the mitochondrial pathway. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Mitochondrial release of cytochrome C forms apoptosomes, activating caspase family enzymes (such as Caspase-9, Caspase-3/6/7), which leads to apoptosis. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | However, survival inhibits this process Apoptosis is essential in determining the response to IM and in the development of drug resistance in GIST. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Although IM strongly inhibits proliferation, it often fails to trigger adequate apoptosis, resulting in low pathological complete response rates and high progression rates in metastatic disease . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Liu et al. reported that IM induces quiescence in some GIST cells, marked by p27(Kip1) upregulation, Cyclin A loss, and G0-G1 arrest . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The DREAM complex also plays a role in maintaining quiescence . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | IM alters apoptotic protein expression, revealing potential therapeutic targets. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Romeo et al. found that p53 and p16 expression independently affect PFS, highlighting the importance of apoptosis/cell cycle balance . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Osteopontin, via β-catenin signaling, upregulates Mcl-1, antagonizing IM-induced apoptosis . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | The FBXW7-Mcl-1 axis regulates IM sensitivity; FBXW7 suppresses Mcl-1 to enhance apoptosis and predict IM response . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Inhibiting BRD9 activates PUMA through the TUFT1/AKT/GSK-3β/p65 axis, enhancing IM-induced apoptosis . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Autophagy is a tightly regulated lysosome-dependent degradation pathway that ensures cellular homeostasis by eliminating damaged organelles, misfolded proteins, and invading pathogens . |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | It is classified into macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | CMA selectively degrades soluble cytosolic proteins harboring a KFERQ-like motif, mediated by the LAMP-2A receptor and Hsp70 [83–85]. |
PMC12065685 | Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors | Macroautophagy, the most studied subtype, involves the formation of double-membraned autophagosomes, which engulf cytoplasmic cargo and fuse with lysosomes for degradation. |
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