PMCID string | Title string | Sentences string |
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PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Twenty-four 4-weeks-old BALB/c nude mice (Vital River Laboratory Animal Co., Ltd., Beijing, China) were animal experiment subjects. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The experiments were approved by the Institutional Animal Care and Use Committee of the Affiliated Hospital of Inner Mongolia Minzu University (n° 201306YT2). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | All animal experiments complied with the ARRIVE guidelines. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | GIST-882 cells (1×10) stably transfected with si-NC and si-circAPP were subcutaneously inoculated into BALB/c nude mice (n = 6/group), and tumor volumes were measured weekly with vernier calipers from the second week after injection. . |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Five weeks later, all mice were euthanized by cervical dislocation under isoflurane (5 %) treatment. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Tumors were resected for immunohistochemistry with antibodies against HK2 (22029-1-AP, Proteintech), PKM2 (15822-1-AP, Proteintech), and Ki-67 (ab15580, Abcam). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | To determine the distant metastasis of tumors, GIST-882 cells (1×10) stably transfected with si-NC and si-circAPP were injected into nude mice via tail vein, and the nude mice were euthanized after 8 weeks to assess liver metastasis by HE-staining. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | All statistical analyses were performed using GraphPad Prism 9.0 (GraphPad Software, CA, USA). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Data represent mean ± Standard Deviation (SD). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Two-tailed Student's t-test and one-way ANOVA determined statistical differences. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Statistical significance represented p < 0.05. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | CircAPP has been revealed to be abnormally expressed in GIST. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Consistent results were also obtained in this study, and circAPP expression in GIST tissues and cell lines was higher than that in normal tissues and cells (Fig. 1A, B). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The circbase database discovered that circAPP is 678 bp in length and consisted of exons 4‒7 of the APP gene located on chromosome 21q21.3 (Fig. 1C). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Examinations of the ring structure of circAPP revealed that RNase R treatment only decreased linear APP mRNA but not circAPP (Fig. 1D). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | After actinomycin D treatment, circAPP had a longer half-life than linear APP mRNA (Fig. 1E). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Subsequently, the location of circAPP in GIST-882 cells was examined by subcellular isolation assay, confirming circAPP mainly expressed in the cytoplasm (Fig. 1F).Fig. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | 1CircAPP is up-regulated in GIST. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | CircAPP in GIST tissues and adjacent normal tissues, (B) CircAPP in GIST cell lines and normal cell lines, (C) Gene structure of circAPP on the circbase database, (D and E) RNaseR and actinomycin D treatment to explore the ring structure of circAPP, (F) Subcellular localization of circAPP; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05.Fig 1 CircAPP is up-regulated in GIST. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | CircAPP in GIST tissues and adjacent normal tissues, (B) CircAPP in GIST cell lines and normal cell lines, (C) Gene structure of circAPP on the circbase database, (D and E) RNaseR and actinomycin D treatment to explore the ring structure of circAPP, (F) Subcellular localization of circAPP; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Since GIST-882 has the highest expression level of circAPP, follow-up studies were performed using GIST-882. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Focusing on the functions of circAPP in GIST, si-circAPP was transected into GIST-882 cells which maintained circAPP expression in a suppressed state (Fig. 2A). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Corresponding to the decrease in circAPP expression, the cloning ability and Edu-positive cell number of GIST-882 cells examined by colony formation assay (Fig. 2B) and EdU assay (Fig. 2C) were reduced, and the apoptosis rate tested by flow cytometry was augmented (Fig. 2D). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | For examining Warburg effect in GIST-882 cells, glucose consumption, lactate production, and ATP levels, along with ATP/ADP and NAD/NADH were the tested indices. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | In circAPP-silenced GIST-882 cells, reduction in glucose consumption, lactate production, ATP, and ATP/ADP, and upregulation of NAD/NADH were detectable (Fig. 2E, F). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Moreover, key Warburg effect proteins HK2 and PKM2 were examined by western blot: after silencing circAPP, HK2 and PKM2 levels were reduced (Fig. 2G), further proving the anti-Warburg effect property of silencing circAPP in GIST.Fig. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | 2Knockdown of circAPP inhibits GIST proliferation and the Warburg effect. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | si-circAPP was transfected into GIST-882 and GES-1 cells. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Expression changes of circAPP, (B and C) Colony formation and EdU assays to assess cell proliferation, (D) Flow cytometry to analyze apoptosis, (E) Cellular glucose consumption, lactate production, and ATP levels, (F) ATP/ADP ratio and NAD/NADH ratio, (G) Western blot to evaluate cellular HK2 and PKM2 protein expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05.Fig 2 Knockdown of circAPP inhibits GIST proliferation and the Warburg effect. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | si-circAPP was transfected into GIST-882 and GES-1 cells. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Expression changes of circAPP, (B and C) Colony formation and EdU assays to assess cell proliferation, (D) Flow cytometry to analyze apoptosis, (E) Cellular glucose consumption, lactate production, and ATP levels, (F) ATP/ADP ratio and NAD/NADH ratio, (G) Western blot to evaluate cellular HK2 and PKM2 protein expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Through the prediction on the bioinformatics website https://starbase.sysu.edu.cn/, circAPP had a potential binding site for miR-6838-5p (Fig. 3A). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Subsequently, this targeting relationship was confirmed, as the results claimed that luciferase activity decreased after co-transfection of WT-circAPP and miR-6838-5p mimic (Fig. 3B); miR-6838-5p and circAPP increased after Ago2 treatment (Fig. 3C). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | RNA gene analysis manifested the reduction of miR-6838-5p in GIST tissues and cells (Fig. 3D, E). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Furthermore, the knockdown of circAPP in GIST-882 cells was also found to promote miR-6838-5p expression (Fig. 3F). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Taken together, circAPP targets the regulation of miR-6838-5p levels. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Fig. 3CircAPP has a binding relationship with miR-6838-5p. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Bioinformatics website to predict the potential targets of circAPP and miR-6838-5p, (B and C) Dual luciferase reporter assay and RIP assay to detect the targeting relationship between circAPP and miR-6838-5p, (D and E) miR-6838-5p expression in tissues and cells, (F) Effect of knockdown of circAPP on miR-6838-5p expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05.Fig 3 CircAPP has a binding relationship with miR-6838-5p. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Bioinformatics website to predict the potential targets of circAPP and miR-6838-5p, (B and C) Dual luciferase reporter assay and RIP assay to detect the targeting relationship between circAPP and miR-6838-5p, (D and E) miR-6838-5p expression in tissues and cells, (F) Effect of knockdown of circAPP on miR-6838-5p expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | To confirm circAPP/miR-838-5p regulating the biological behavior of GIST, miR-6838-5p inhibitor and si-circAPP were transfected into GIST-882 cells. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Transfection of si-circAPP alone miR-6838-5p expression, but the action of si-circAPP was impaired by miR-6838-5p inhibitor (Fig. 4A). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Functional experiments showed (Fig. 4B‒G) that transfection of miR-6838-5p inhibitor alone enhanced the clonality and proliferation, decreased apoptosis rate, and promoted cellular glucose consumption, lactate production, ATP and ATP/ADP, downregulated NAD/NADH, and induced HK2 and PKM2 protein expression. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | si-circAPP showed opposite effects which could be blocked by co-transfection of miR-6838-5p inhibitor. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | All in all, circAPP affects GIST proliferation and the Warburg effect by regulating miR-6838-5p expression. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Fig. 4miR-6838-5p inhibitor promotes GIST proliferation and the Warburg effect and reverses the effect of si-circAPP. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | miR-6838-5p inhibitor was transfected alone or si-circAPP and miR-6838-5p inhibitor were co-transfected, (A) Expression changes of miR-6838-5p, (B and C) Colony formation and EdU assays to assess cell proliferation, (D) Flow cytometry to analyze apoptosis, (E) Cellular glucose consumption, lactate production, and ATP levels, (F) ATP/ADP ratio and NAD/NADH ratio, (G) Western blot to evaluate cellular HK2 and PKM2 protein expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05.Fig 4 miR-6838-5p inhibitor promotes GIST proliferation and the Warburg effect and reverses the effect of si-circAPP. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | miR-6838-5p inhibitor was transfected alone or si-circAPP and miR-6838-5p inhibitor were co-transfected, (A) Expression changes of miR-6838-5p, (B and C) Colony formation and EdU assays to assess cell proliferation, (D) Flow cytometry to analyze apoptosis, (E) Cellular glucose consumption, lactate production, and ATP levels, (F) ATP/ADP ratio and NAD/NADH ratio, (G) Western blot to evaluate cellular HK2 and PKM2 protein expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The bioinformatics website starbase predicted the existence of potential binding sites for miR-6838-5p and CDV3 (Fig. 5A). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Co-transfection of WT-CDV3 and miR-6838-5p mimic inhibited luciferase activity (Fig. 5B); CDV3 and miR-6838-5p were enriched with Ago2 (Fig. 5C). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | CDV3 was higher in both GIST tissues and cell lines than in normal tissues and cell lines (Fig. 5D, E). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Furthermore, miR-6838-5p mimics suppressed CDV3 expression in GIST (Fig. 5F). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Shortly, CDV3 is modified by miR-6838-5p. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Fig. 5CDV3 is a target of miR-6838-5p. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Bioinformatics website to predict the potential targets of CDV3 and miR-6838-5p, (B and C) Dual luciferase reporter assay and RIP assay to detect the targeting relationship between CDV3 and miR-6838-5p, (D and E) CDV3 expression in tissues and cells, (F) Effect of miR-6838-5p on CDV3 expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05.Fig 5 CDV3 is a target of miR-6838-5p. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Bioinformatics website to predict the potential targets of CDV3 and miR-6838-5p, (B and C) Dual luciferase reporter assay and RIP assay to detect the targeting relationship between CDV3 and miR-6838-5p, (D and E) CDV3 expression in tissues and cells, (F) Effect of miR-6838-5p on CDV3 expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | To investigate circAPP/miR-6838-5p/CDV3 affecting GIST biological behavior, this study co-transfected pcDNA 3.1-circAPP and si-CDV3 into GIST-882 cells. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Changes in miR-6838-5p and CDV3 expression were examined. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | pcDNA 3.1-circAPP inhibited miR-6838-5p and elevated CDV3 levels, while si-CDV3 had no effect on miR-6838-5p expression but reversed CDV3 expression (Fig. 6A, B). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The functional rescue of pcDNA 3.1-circAPP by si-CDV3 was subsequently confirmed in the aspects of clonality, the number of Edu-positive cells, apoptosis rate, cellular glucose consumption, lactate production, ATP levels, ATP/ADP ratio, NAD/NADH ratio, HK2 and PKM2 protein expression (Fig. 6C‒H). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Taken together, circAPP promotes GIST proliferation and the Warburg effect via the miR-6838-5p/CDV3 axis. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Fig. 6CircAPP promotes GIST proliferation and the Warburg effect by regulating the miR-6838-5p/CDV3 axis. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | pcDNA 3.1-circAPP and si-CDV3 were co-transfected, (A) Expression changes of miR-6838-5p, (B) Expression changes of CDV3, (C and D) Colony formation and EdU assays to assess cell proliferation, (E) Flow cytometry to analyze apoptosis, (F) Cellular glucose consumption, lactate production, and ATP levels, (G) ATP/ADP ratio and NAD/NADH ratio, (H) Western blot to evaluate cellular HK2 and PKM2 protein expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05.Fig 6 CircAPP promotes GIST proliferation and the Warburg effect by regulating the miR-6838-5p/CDV3 axis. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | pcDNA 3.1-circAPP and si-CDV3 were co-transfected, (A) Expression changes of miR-6838-5p, (B) Expression changes of CDV3, (C and D) Colony formation and EdU assays to assess cell proliferation, (E) Flow cytometry to analyze apoptosis, (F) Cellular glucose consumption, lactate production, and ATP levels, (G) ATP/ADP ratio and NAD/NADH ratio, (H) Western blot to evaluate cellular HK2 and PKM2 protein expression; data are expressed as mean ± SD (n = 3). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | This study examined the effect of circAPP on GIST tumor growth and liver metastasis in vivo. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | As demonstrated in Fig. 7A-C, ablating circAPP suppressed GIST tumor volume and weight. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Immunohistochemistry showed that circAPP knockdown suppressed HK2, PKM2, and Ki-67 in GIST tumors (Fig. 7D). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Furthermore, knockdown of circAPP suppressed CDV3 expression in tumors (Fig. 7E). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Liver metastasis of GIST tumors was assessed by HE-staining (Fig. 7F), manifesting that circAPP depletion suppressed the number of metastatic nodules in the liver. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | circAPP mediates GIST tumor growth and metastasis. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Fig. 7CircAPP inhibits GIST tumor growth and metastasis in vivo. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Representative image of tumors, (B) Tumor volume, (C) Tumor weight, (D) IHC image of HK2, PKM2, and Ki-67 proteins in tumors, (E) Western blot detection of tumor CDV3 expression, (F) HE images of tumor liver metastases; data are expressed as mean ± SD (n = 6). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05.Fig 7 CircAPP inhibits GIST tumor growth and metastasis in vivo. ( |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Representative image of tumors, (B) Tumor volume, (C) Tumor weight, (D) IHC image of HK2, PKM2, and Ki-67 proteins in tumors, (E) Western blot detection of tumor CDV3 expression, (F) HE images of tumor liver metastases; data are expressed as mean ± SD (n = 6). * |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | p < 0.05. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | GIST accounts for 1 %‒3 % of gastrointestinal tumors. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | CircRNAs are imperative regulators in various physiological processes and the occurrence of GIST. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | This study found that circAPP expression was augmented in GIST, and knocking down circAPP hampered GIST cell proliferation and the Warburg effect, triggered cell apoptosis, and limited GIST tumor growth and liver metastasis. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | CircRNAs have become a research hotspot in recent years. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | As research progresses, the functions and mechanistic network of circRNAs in cancer have been implicated in tumor cell activities, including Warburg effect. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The Warburg effect, proposed by Dr. Otto Heinrich Warburg in 1920, refers to the shift of tumor cell metabolism from oxidative phosphorylation to aerobic glycolysis induced by mitochondrial respiration damage. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The Warburg effect is a central contributor to the mechanisms of cancer progression, contributing to the cellular progression of cancer cells and being involved in immune responses and drug resistance. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Therefore, inhibiting the Warburg effect inhibits cancer progression. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | This study confirms that circAPP was a positive regulator of the Warburg effect. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Similar to a previous report, this study also presented that circAPP was overexpressed in GIST. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The in vitro results reported that downregulating circAPP inhibited GIST cell proliferation and the Warburg effect. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Distant metastasis has been reported to be obstructive to cancer treatment. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Therefore, this study further verified the suppressive impacts of silencing circAPP on GIST tumor growth and liver metastasis in vivo. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | miRNA sponging is the most well-studied mechanism of circRNA action, and circRNA competitively binds miRNA through complementary base pairing to inhibit the binding of miRNA to its target molecule, thereby regulating the expression of target Mrna. |
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