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Updated: Jun 12, 2025

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and
Fang-Wen Zou1, Yi-Fang Tang2, Xiaojing Li3
1Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, P.R. China.
Abstract:
Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are implicated in the development and progression of various tumors. The aim of this study was to investigate the effects of circ_SMA4 in Gastrointestinal Stromal Tumors (GISTs) malignant progression. Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in GISTs. The effect of circ_SMA4 on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo settings. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_SMA4/miR-494-3p/ KIT axis. The results revealed that circ_SMA4 was significantly upregulated in GISTs, and exhibited high diagnostic efficiency with an AUC of 0.9824 (P < 0.01). circ_SMA4 promoted cell proliferation, invasion, migration, while inhibiting apoptosis in GISTs cells, both in vitro and in vivo. Silencing circ_SMA4 partially inhibited GISTs malignant progression. Additionally, circ_SMA4 acted as a competing endogenous RNA (ceRNA) by targeting miR-494-3p, and KIT was identified as a functional gene for miR-494-3p in GISTs. Furthermore, the results confirmed that circ_SMA4/miR-494-3p/ KIT axis plays a role in activating the JAK/STAT signaling pathway in GISTs. Therefore, for the first time, we have identified and emphasized that circ_SMA4 is significantly upregulated and plays an oncogenic role in GISTs by sponging miR-494-3p to activate the KIT/JAK/STAT pathway. These findings underscore circ_SMA4 may serve as a novel diagnostic biomarker and therapeutic target for GISTs.
Insights
Circular RNA circ_SMA4 is upregulated in Gastrointestinal Stromal Tumors (GISTs), promoting cancer progression and acting as a potential diagnostic biomarker. It influences cell growth, migration, and apoptosis via the circ_SMA4/miR-494-3p/KIT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in tumor development.
- Aberrant expression of circRNAs is linked to various cancers, including Gastrointestinal Stromal Tumors (GISTs).
Purpose of the Study:
- To investigate the role of circ_SMA4 in the malignant progression of GISTs.
- To explore circ_SMA4 as a potential diagnostic biomarker and therapeutic target for GISTs.
Main Methods:
- Human circRNAs microarray analysis to identify differentially expressed circRNAs.
- In vitro and in vivo assays to assess circ_SMA4's effects on GIST cell behavior (proliferation, invasion, migration, apoptosis).
- Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assays to elucidate the circ_SMA4/miR-494-3p/KIT axis and JAK/STAT pathway activation.
Main Results:
- circ_SMA4 was significantly upregulated in GISTs with high diagnostic efficiency (AUC=0.9824).
- circ_SMA4 promoted GIST cell proliferation, invasion, and migration while inhibiting apoptosis.
- circ_SMA4 functions as a competing endogenous RNA (ceRNA) for miR-494-3p, targeting the KIT gene and activating the JAK/STAT pathway.
Conclusions:
- circ_SMA4 plays a significant oncogenic role in GISTs.
- The circ_SMA4/miR-494-3p/KIT axis is crucial for GIST progression by activating the JAK/STAT pathway.
- circ_SMA4 represents a promising diagnostic biomarker and therapeutic target for GISTs.
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