A therapeutical insight into the correlation between circRNAs and signaling pathways involved in cancer pathogenesis

Saleh, Raed Obaid; Al-Hawary, Sulieman Ibraheem Shelash; Jasim, Saade Abdalkareem; Bokov, Dmitry Olegovich; Hjazi, Ahmed; Oudaha, Khulood H.; Alnajar, Mohammed Jawad; Jumaa, Sally Salih; Alawadi, Ahmed; Alsalamy, Ali

doi:10.1007/s12032-023-02275-4

Med Oncol

2024

DOI: 10.1007/s12032-023-02275-4

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A therapeutical insight into the correlation between circRNAs and signaling pathways involved in cancer pathogenesis

Raed Obaid Saleh,

Sulieman Ibraheem Shelash Al-Hawary,

Saade Abdalkareem Jasim

et al.

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circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway

Zou,

Tang,

et al. 2024

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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. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-73393-w.

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circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway

Zou,

Tang,

et al. 2024

Sci Rep

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A therapeutical insight into the correlation between circRNAs and signaling pathways involved in cancer pathogenesis

Cited by 1 publication

References 104 publications

circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway

circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway

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