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PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Establishment of xenograft tumor model in nude mice.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
After 5 weeks of feeding, the mice were euthanized, and nude mice were taken out to measure their size and weighed. (
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Xenograft tumor growth curves and (C) Xenograft tumor weight revealed that circ_SMA4 promotes GISTs cell proliferation in vivo. (
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
The percentage of Ki67-positive cells in xenograft tumors was measured. (
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
TUNEL assay was performed to determine the cell apoptosis rate in Xenograft tumors.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
The expression of circ_SMA4 (F), miR-494-3p (G) and KIT mRNA (H) in Xenograft tumors were detected by RT-qPCR assay.n = 3. *
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
P < 0.05, **P < 0.01, na: no statistical significance.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
RT-qPCR, reverse transcription- quantitative PCR.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
OE: OverExpression.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
shRNA: short hairpin RNA.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
NC: negative control.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
OD, Optical Density.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
circ_SMA4: circ_103870.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Moreover, TUNEL apoptosis assays conducted with xenograft tumor samples provided evidence that circ_SMA4 overexpression inhibited apoptosis in GIST-T1 cells in vivo, while circ_SMA4 silencing promoted apoptosis in GIST-882 cells in vivo (P < 0.05; Fig. 8E).
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Additionally, the RT-qPCR assay unveiled a significant upregulation of circ_SMA4 and KIT mRNA expression of xenograft tumor samples in the circ_SMA4 overexpressing group, accompanied by a marked downregulation in the sh-circ_SMA4 group (P < 0.05; Fig. 8F/H).
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Conversely, miR-494-3p expression of xenograft tumor samples exhibited a significant downregulation in the circ_SMA4 overexpressing group and a substantial upregulation in the sh-circ_SMA4 group (P < 0.05; Fig. 8G).
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
These comprehensive findings, consistent with the in vitro results, strongly suggest that circ_SMA4 plays a pivotal oncogenic role in GISTs in vivo.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Gastrointestinal stromal tumors (GISTs) are a diverse group of tumors found throughout the gastrointestinal tract, varying in malignancy.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Initially categorized as smooth muscle tumors, they were later reclassified as gastric stromal tumors due to atypical smooth muscle differentiation observed in some cases.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
GISTs are now recognized as originating from interstitial cells of Cajal, leading to their classification as mesenchymal tumors emerging in the submucosa.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
This reclassification marked a new era, with reports before 1993 predominantly referring to GISTs when discussing gastric and intestinal smooth muscle tumors.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
The primary approach for GISTs typically involves radical surgical intervention, which remains the cornerstone of treatment.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Complete resection of the tumor, whenever feasible, is the preferred strategy as it offers the best chance for long-term disease control and potentially even cure.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
However, for patients with advanced or metastatic disease, especially those harboring c-kit and/or PDGFRα mutations, additional therapeutic modalities are often necessary.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
In recent years, molecular targeted therapies have revolutionized the management of GISTs, particularly for patients who are not amenable to surgery or who have recurrent or metastatic disease.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Imatinib, a tyrosine kinase inhibitor, has emerged as a pivotal therapeutic agent in this context.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
By selectively inhibiting the activity of mutant c-kit and PDGFRα receptors, imatinib effectively suppresses tumor growth and prolongs survival in these patients.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Its success in clinical trials has led to its widespread adoption as a first-line treatment for advanced GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Despite the efficacy of targeted therapies like imatinib, challenges persist in accurately diagnosing and predicting the behavior of GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Currently, the repertoire of effective tumor biomarkers for GISTs diagnosis and prognostication remains limited.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
This underscores the need for ongoing research efforts aimed at identifying novel biomarkers that can aid in early detection, risk stratification, and treatment optimization for patients with GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Additionally, the development of personalized medicine approaches, tailored to the specific molecular characteristics of individual tumors, holds promise for further improving outcomes in this challenging disease landscape.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Circular RNAs (circRNAs) are significant contributors to cancer biology, playing diverse roles in tumorigenesis, tumor progression, and metastasis.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
These non-coding RNAs feature a covalently closed loop structure, making them resistant to exonucleases and providing stability.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Dysregulated expression patterns of circRNAs in various cancer types compared to normal tissues underscore their relevance in cancer.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Studies suggest circRNAs act as competing endogenous RNAs (ceRNAs), sequestering microRNAs (miRNAs) to relieve repression of miRNA target genes, thereby promoting oncogenic signaling pathways.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Additionally, circRNAs interact with RNA-binding proteins (RBPs), influencing RNA processing, stability, and translation, contributing to cancer pathogenesis.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Recent researches highlights the involvement of circRNAs in GISTs, influencing tumorigenesis, progression, and metastasis.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Dysregulated expression of circRNAs in GISTs compared to normal gastrointestinal tissues suggests their potential as diagnostic or prognostic biomarkers.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
CircRNAs modulate key cellular processes in GISTs development, including proliferation, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT), functioning as ceRNAs by sequestering miRNAs and influencing target gene expression in oncogenic pathways.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Aberrant circRNA expression correlates with clinicopathological features, tumor stage, metastasis, and patient prognosis in GISTs, suggesting their utility as potential biomarkers for diagnosis, prognosis, and therapeutic response prediction.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
In summary, circRNAs play significant roles in GISTs pathogenesis and may serve as novel targets for diagnosis, prognosis, and therapeutic intervention.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Further research is needed to elucidate the specific roles and underlying mechanisms of circRNAs in GISTs tumorigenesis and progression.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Our preliminary study revealed that circ_SMA4 (hsa_circRNA_103870) was significantly up-regulated in GISTs (n = 20), and circ_SMA4 also showed high diagnostic values, and significantly associated with tumor size, mitotic figure, and malignant degrees in GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
In this study, we established circ_SMA4 overexpression and knockdown cell models to investigate its effects on the biological behavior of GISTs cells.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Our findings revealed that circ_SMA4 promotes cell proliferation, invasion, and migration while inhibiting apoptosis in GISTs cells, both in vitro and in vivo.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Silencing circ_SMA4 partially inhibited the malignant progression of GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
As far as we know, this is the first such report for the oncogene role of circ_SMA4 in GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Additionally, through querying the circBase database, we identified has_circRNA_103870 (circBase ID: hsa_circ_0072805) located on chromosome 5:69206201–69,206,389, representing one of the most prevalent circRNAs derived from exons and associated with the gene symbol SMA4.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
To date, there are no reports on circ_SMA4 (has_circRNA_103870) in the current literature.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Moreover, our study elucidated the molecular mechanism underlying the oncogenic function of circ_SMA4 in GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Current research suggests that circRNAs primarily function as competitive endogenous RNAs (ceRNAs) by binding to microRNAs (miRNAs), thereby silencing or degrading the target miRNAs and relieving their regulation on downstream target genes, thus exerting regulatory functions.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
We identified circ_SMA4 as a ceRNA that binds to miR-494-3p, thereby sequestering it and relieving its suppression of KIT expression.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
More recently, miR-494-3p has emerged as a significant member of the miR-494 family.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
It originates from the 3’-arm of the miR-494 precursor and is located on chromosome 12q32.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Current research indicates that miR-494-3p primarily participates as a tumor suppressor gene in the occurrence, development, and drug resistance processes of cancer.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
For instance, Faversani et al. found that miR-494-3p is a novel driver of lung carcinogenesis.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Kim et al. reported that RAS-stimulated release of exosomes miR-494-3p promotes the osteolytic bone metastasis of breast cancer cells.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Kaźmierczak et al. reported that elevated expression of miR-494-3p is associated with resistance to Osimertinib in EGFR T790M-positive NSCLC.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
However, there is currently no research on miR-494-3p in GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Our study confirmed the tumor-suppressive role of miR-494-3p in GISTs through circ_SMA4, further substantiating the critical role of the miR-494-3p family in cancer regulation.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Furthermore, KIT, a well-known oncogene in GISTs, was confirmed as a functional target of miR-494-3p in GISTs cells.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Our research findings indicate that circ_SMA4-induced silencing of miR-494-3p results in the activation of KIT.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
KIT, also known as c-KIT, located on chromosome 4q12, is an oncogene that encodes a type III transmembrane receptor tyrosine kinase with tyrosine kinase activity.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
The receptor tyrosine kinase c-KIT dimerizes and autophosphorylates upon binding with its ligand stem cell factor (SCF), also known as mast cell growth factor (MGF).
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
The genetic underpinning of GISTs growth involves activation of c-KIT, resulting in the constitutional activation of receptor tyrosine kinases, serving as the driving force behind tumor development.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Activation of c-KIT enhances intracellular signaling through JAK/STAT pathways ultimately leading to cell proliferation and survival.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Our research further reveals that upon activation of KIT, the JAK/STAT signaling pathway is further activated in GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
The JAK/STAT signaling pathway plays a crucial role in the occurrence and development of GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Activation of this pathway, often initiated by aberrant KIT signaling due to mutations, leads to the phosphorylation and activation of Janus kinases (JAK) and subsequent phosphorylation of Signal Transducer and Activator of Transcription (STAT) proteins.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
These activated STAT proteins then translocate to the nucleus, where they regulate the transcription of target genes involved in cell proliferation, survival, and differentiation.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Dysregulation of the JAK/STAT pathway contributes to the uncontrolled growth and survival of GISTs cells, making it a significant pathway for targeted therapeutic interventions in GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Based on our current research evidence, it is evident that during the occurrence and progression of GISTs, circ_SMA4 is activated.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Upregulation of circ_SMA4 leads to the silencing or degradation of its target miR-494-3p, thereby relieving the inhibition on its target gene KIT, resulting in the activation of KIT.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
The activated KIT gene further activates downstream signaling pathways, particularly the JAK/STAT pathway, ultimately driving the malignant progression of GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
However, whether the activation of KIT by circ_SMA4 is correlated with KIT gene mutations (from quantitative to qualitative changes), or if the activation of KIT by circ_SMA4 may represent an adaptive response before KIT gene mutations in GISTs, remains uncertain and warrants further investigation.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Nonetheless, the functional role of the circ_SMA4/miR-494-3p/KIT/JAK/STAT pathway in the occurrence and development of GISTs is clearly established.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
These findings have several important implications.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Firstly, our study highlights circ_SMA4 as a potential diagnostic biomarker for GISTs, given its consistent upregulation in GISTs tissues.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Detection of circ_SMA4 levels may aid in the early diagnosis and monitoring of GISTs patients.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Secondly, targeting circ_SMA4 or its downstream signaling pathway, such as the miR-494-3p/ KIT/JAK/STAT axis, may offer a promising therapeutic strategy for GISTs treatment.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Inhibition of circ_SMA4 expression or interference with its interaction with miR-494-3p could potentially suppress GISTs cell proliferation and metastasis, providing a new avenue for therapeutic intervention.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
However, there are several limitations to our study.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
First, only 20 patients were enrolled in our study, which makes the sample size relatively small, and the results show an association rather than a definite causal relationship.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Additionally, the analysis of the relationship between clinical factors and circRNAs needs to be supported by larger samples.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Secondly, the critical circRNA circ_SMA4 chosen in this study has numerous downstream target miRNAs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
We only observed the effect of circ_SMA4 on miR-494-3p, which is a significant limitation.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Thirdly, in terms of the regulation of downstream gene signaling pathways of KIT, our research mainly focused on the JAK/STAT signaling pathway.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Other pathways, such as the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways, were not further explored.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Furthermore, although current research suggests that most circular RNAs are predominantly enriched in the cytoplasm, we did not explicitly determine the localization of circ_SMA4 in this study.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
In future research, we plan to further clarify the subcellular localization of circ_SMA4 using ISH and nucleocytoplasmic separation techniques.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Therefore, in our future work, further studies with larger groups of patients, the improvement of the circ_SMA4-miRNA-mRNA regulatory network, and further validation in vivo and in vitro also need to be explored.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
In summary, our study marks the first comprehensive exploration into the role of circ_SMA4 in GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
We have underscored its significant upregulation and unveiled its oncogenic function in GISTs, where it acts by sequestering miR-494-3p, thereby activating the KIT/JAK/STAT pathway.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
These findings illuminate circ_SMA4’s potential as a novel diagnostic biomarker and therapeutic target for GISTs.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
However, further investigation into the precise mechanisms by which circ_SMA4 mediates oncogenesis in GISTs is imperative to fully realize its clinical implications and therapeutic potential.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
Furthermore, as our understanding of the intricate regulatory roles of circRNAs continues to evolve, there lies the promise of unveiling innovative strategies to enhance the efficacy of targeted therapies for GISTs patients.
PMC11422497
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway
To fully harness the clinical significance of circRNAs in this context, additional research efforts and clinical validation are essential.
PMC12852540
Choosing the right animal model for sarcoma research
Sarcomas comprise over 100 mesenchymal malignancies characterised by extreme genomic heterogeneity, ranging from fusion-driven paediatric tumours to highly unstable adult leiomyosarcomas.
PMC12852540
Choosing the right animal model for sarcoma research
This genetic complexity shapes tumour behaviour, influences growth and metastasis, and determines how patients respond to therapy.