Tip of the Iceberg: Roles of CircRNAs in Cancer Glycolysis

Tan, Li; Xian, Hong-chun; Dai, Li; Tang, Yaling; Liang, Xin‐hua

doi:10.2147/ott.s297140

Cited by 15 publications

(10 citation statements)

References 112 publications

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“…Targeting LDHA promotes DTX-induced cytotoxicity predominantly in castration-resistant PCa cells (37). Besides, several studies have revealed that circRNAs can regulate the cancer metabolism process by affecting the expression of glycolysis-relevant enzymes and pathways (38). In this study, we found that circARHGAP29 could promote LDHA-mediated cell proliferation and glycolysis in DTX-resistant PCa cells by binding to the IGF2BP2 protein.…”

Section: Discussionmentioning

confidence: 61%

EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling

et al. 2022

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Docetaxel-based chemotherapy is a standard-of-care treatment for metastatic prostate cancer (PCa), and chemoresistance remains a major challenge in clinical practice. Recent studies have demonstrated that circular RNAs (circRNAs) play critical roles in the development and progression of PCa. However, the biological roles and potential functions of circRNAs in mediating docetaxel-resistant PCa have yet to be well elucidated. In this study, we analyzed the expression profiles of circRNAs in docetaxel-resistant and -sensitive PCa cells through RNA sequencing and found that expression of circARHGAP29 was significantly upregulated in docetaxel-resistant cell lines and clinical samples. Ectopic expression of circARHGAP29 triggered docetaxel resistance and aerobic glycolysis in PCa cells, which was reduced by silencing circARHGAP29. Moreover, eukaryotic initiation factor 4A3 (EIF4A3), which bound the back-spliced junction site and the downstream flanking sequence of circARHGAP29, induced cyclization and cytoplasmic export of circARHGAP29. circARHGAP29 increased the stability of lactate dehydrogenase A (LDHA) mRNA by strengthening its interaction with insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), leading to enhanced glycolytic metabolism. In addition, circARHGAP29 interacted with and stabilized c-Myc mRNA and protein, which further increased LDHA expression by facilitating its transcription. These findings reveal the crucial function of circARHGAP29 in PCa glycolysis by increasing and stabilizing LDHA mRNA, providing a promising therapeutic target in docetaxel-resistant PCa. SignificanceUpregulation of a novel circRNA, circARHGAP29, promotes docetaxel resistance and glycolytic metabolism, suggesting it could be a prognostic biomarker and therapeutic target in chemoresistant prostate cancer.Research.

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Section: Discussionmentioning

confidence: 61%

EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling

et al. 2022

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“…Compared with other lines, it is highly conservative. Most circular RNAs are abundant, stable, and conservative and often indicate tissue/developmental stage-specific patterns [ 22 ]. More circular RNA disorders are involved in several biological processes of malignant tumors, such as tumorigenesis, growth, invasion, metastasis, apoptosis, and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ-ABCB10 Promotes Proliferation and Inhibits Apoptosis of Laryngeal Carcinoma by Inhibiting KLF6

Chen

Zhang

Zhao

2022

Computational and Mathematical Methods in Medicine

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Objective. To explore the effect of circular RNA circ-ABCB10 on the proliferation and apoptosis of laryngeal carcinoma via inhibiting KLF6. Methods. RT-qPCR assay was adopted to detect the expression of circ-ABCB10 and KFL6 in laryngeal carcinoma tissues and cell lines. Cell counting kit-8 (CCK-8) and clone formation assay were employed to detect laryngeal cancer cell viability and proliferation when circ-ABCB10 was silenced or upregulated. In this study, the apoptosis rate was detected by flow cytometry and the protein expression was detected by Western blotting. Wound healing and cross-hole invasion were used to study the migration and invasion of laryngeal cancer cells when circ-ABCB10 was silenced or upregulated. Results. The results of RT-qPCR detection indicated that the expression of circ-ABCB10 in all three laryngeal carcinoma cells was downregulated by 3.2 times compared with that of HaCat cells. There is low expression of circ-ABCB10 in most laryngeal carcinoma tissues, the diagnostic cutoff value of circ-ABCB10 is 0.0008, the area under the curve is 0.718, the sensitivity is 0.981, and the specificity is 0.556. The expression level of KLF6 in laryngeal carcinoma is on the rise, which is significantly higher compared to healthy tissues ( P < 0.05 ); 48 hours after transfection, RT-qPCR analysis confirmed the transfection efficiency, and upregulation of circ-ABCB10 could significantly promote cell proliferation. Compared with the control group, silencing circ-MTCL1 could inhibit cell proliferation, overexpression of circ-ABCB10 promoted cell migration, and downregulation of circ-ABCB10 significantly inhibited cell movement ( P < 0.001 ). Upregulation of circ-ABCB10 significantly enhanced the invasiveness and motility of laryngeal cancer cells, while downregulation of circ-ABCB10 was the opposite. Compared with the KLF6 NC group, KLF6 level increased significantly in the KLF6 group, while cell viability, colony formation, scratch healing rate, invasive cell number, and Bcl-2 expression level decreased significantly in the KLF6 group, while apoptosis rate and Bax expression level increased significantly ( P < 0.05 ). KLF6 level in the si-circ-ABCB10+anti-KLF6 group was significantly lower than that in the si-circ-ABCB10+anti-KLF6-NC group ( P < 0.05 ). Meanwhile, the cell activity, colony formation number, cell scratch healing rate, number of invaded cells, and Bcl-2 all indicated an upward trend, while the cell apoptosis rate and Bax expression indicated a downward trend ( P < 0.05 ). Conclusion. The expression of circ-ABCB10 in laryngeal carcinoma was significantly higher compared to that in paracancerous tissues. Silencing circ-ABCB10 could significantly inhibit the growth and proliferation of laryngeal adenocarcinoma cells, while overexpression of circ-ABCB10 could significantly promote the growth of laryngeal adenocarcinoma cells, probably by inhibiting KLF6 to enhance the proliferation of laryngeal carcinoma and inhibit apoptosis.

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“…Under physiological conditions, neurons mainly use most of the glucose to produce ATP through the pentose-phosphate pathway (PPP), while the glycolysis state is low [ 11 ]. When cerebral I/R occurs, neuronal glucose metabolism converts from PPP to glycolysis, which is induced by the increased expression of the glycolytic promoting enzymes such as lactate dehydrogenase A (LDHA), glucose transporter1 (GLUT1), and hexokinase2 (HK2) [ 11 , 12 ]. Enhancement of glycolysis also can lead to higher glucose consumption, more lactic acid accumulation, and less ATP production, which ultimately accelerates neuronal death [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Celastrol Protects against Cerebral Ischemia/Reperfusion Injury in Mice by Inhibiting Glycolysis through Targeting HIF-1α/PDK1 Axis

Liu

Luo

Cao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cerebral ischemia/reperfusion (I/R) injury is closely related to dysfunctional glucose metabolism. Celastrol is a bioactive compound that has been found to exhibit neuroprotective effects in cerebral ischemia, while whether it can protect against cerebral I/R injury by regulating glycolysis remains unclear. The goal of this study is to investigate the role of celastrol on cerebral I/R injury and its underlying mechanisms in transient middle cerebral artery occlusion (tMCAO) mice. Methods. To observe the protective effect of celastrol and select its optimal dosage for further study, neurological score, TTC staining, and HE staining were used to evaluate neurological function, cerebral infarct volume, and cortical cell damage, respectively. QRT-PCR and Western blot were used to detect the mRNA and protein expression of hypoxia inducible factor-1α (HIF-1α), pyruvate dehydrogenasekinase1 (PDK1), lactate dehydrogenase A (LDHA), glucose transporter1 (GLUT1), and hexokinase2 (HK2), respectively. The lactate production, ATP level, and glucose content were assessed by assay kits. Results. Our results indicated that celastrol dose-dependently improved neurological function and reduced cerebral infarct volume and cortical cell death of tMCAO mice, and its optimal dosage was 4.5 mg/kg. In addition, celastrol significantly blocked I/R-induced increase of LDHA, GLUT1, HK2, and lactate production as well as decrease of ATP level and glucose content. Moreover, celastrol inhibited the I/R-induced upregulation of HIF-1α and PDK1. Overexpression of HIF-1α by DMOG reversed the protective effect of celastrol on cerebral I/R injury and blocked celastrol-induced suppression of glycolysis. Conclusions. Taken together, these results suggested that celastrol protected against cerebral I/R injury through inhibiting glycolysis via the HIF-1α/PDK1 axis.

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Tip of the Iceberg: Roles of CircRNAs in Cancer Glycolysis

Cited by 15 publications

References 112 publications

EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling

EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling

Circular RNA circ-ABCB10 Promotes Proliferation and Inhibits Apoptosis of Laryngeal Carcinoma by Inhibiting KLF6

Celastrol Protects against Cerebral Ischemia/Reperfusion Injury in Mice by Inhibiting Glycolysis through Targeting HIF-1α/PDK1 Axis

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