Mitochondrial miR-181a-5p promotes glucose metabolism reprogramming in liver cancer by regulating the electron transport chain

Zhuang, Xiang; Chen, Yuwei; Wu, Zhenru; Xu, Qing; Chen, Menglin; Shao, Meiying; Cao, Xinhui; Zhou, Yongjie; Xie, Mingjun; Shi, Yujun; Zeng, Yong; Bu, Hong

doi:10.1093/carcin/bgz174

Cited by 45 publications

(35 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[ 25 ] Cohen and Kesler [ 26 ] have found that mitochondrial dysfunctions, encompassing complexes I–IV of the electron transport chain, are characteristics of PD. MT-CYB , encodes the core subunit of complex III, plays a critical role in promoting progression and development of liver cancer, [ 27 ] and is an essential part of the oxidative phosphorylation system, which arouses cellular homeostasis and energy production. [ 28 ] The expression of MT-ND1 is reduced in Parkinson disease with dementia (PDD).…”

Section: Discussionmentioning

confidence: 99%

RNA-sequencing of peripheral blood circular RNAs in Parkinson disease

Kong

Wang

et al. 2021

Medicine

View full text Add to dashboard Cite

Background: Circular RNAs (circRNAs) play an important role in many neurological diseases and can serve as biomarkers for these diseases. However, the information about circRNAs in Parkinson disease (PD) remained limited. In this study, we aimed to determine the circRNAs expression profile in PD patients and discuss the significance of circRNAs in the diagnosis of PD. Methods and Results: Using RNA-sequencing in peripheral blood RNAs, we showed that a significant number of mRNAs or circRNAs were differentially expressed between PD patients and normal controls (NCs), which included 273 up-regulated and 493 down-regulated mRNAs, and 129 up-regulated and 282 down-regulated circRNAs, respectively. Functional analysis was performed using the Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis, and the results showed that the second most enriched KEGG pathway was PD. These data suggest that the levels of mRNAs and circRNAs in peripheral blood could be potentially used as biomarkers for PD. In addition, we correlated mRNAs and circRNAs by constructing a competing endogenous RNA (ceRNA) network in PD. The resulted-in ceRNA network included 10 differentially expressed mRNAs from PD pathway, 13 predicted miRNAs, and 10 differentially expressed circRNAs. Conclusion: Collectively, we first characterized the expression profiles of circRNAs and mRNAs in peripheral blood from PD patients and proposed their possible characters in the pathogenesis of PD. These results provided valuable insights into the clues underlying the pathogenesis of PD.

show abstract

Section: Discussionmentioning

confidence: 99%

RNA-sequencing of peripheral blood circular RNAs in Parkinson disease

Kong

Wang

et al. 2021

Medicine

View full text Add to dashboard Cite

show abstract

“…The Warburg effect confers a growth advantage on cancer cells and HK2 has a vital role in this process (9,19). High expression levels of HK2 have been observed in LC cells (20,21). HK2 was here revealed to accelerate LC cell proliferation and glycolytic metabolism, as evidenced by an increase in mitochondrial respiration, and decreases in glucose uptake capacity, lactic acid content, glycolytic flux and proliferation in HepG2 cells following transfection with si-HK2.…”

Section: Discussionmentioning

confidence: 73%

HK2 is associated with the Warburg effect and proliferation in liver cancer: Targets for effective therapy with glycyrrhizin

et al. 2021

View full text Add to dashboard Cite

Glycyrrhizin (GA) is the most essential active ingredient in licorice root, and has a wide range of biological and pharmacological activities. The present study aimed to conduct a detailed analysis of the effects of GA on liver cancer (LC) cell proliferation and the Warburg effect. Hexokinase-2 (HK2) is a glycolytic enzyme that catalyzes the Warburg effect. To this end, the LC HepG2 cell line was transfected with small interfering RNA-HK2 or pCDNA3.1-HK2, followed by GA treatment. A Cell Counting Kit-8 assay and EdU staining were employed to evaluate the proliferation rate of LC cells. The expression levels of HK2 and the phosphorylation level of AKT were measured by reverse transcription-quantitative PCR and western blotting, respectively. Furthermore, the glucose uptake capacity and lactic acid content were assessed by kits, and the glycolysis level was evaluated by assessing the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). A pronounced increase in the OCR, and decreases in the cell proliferation, glucose uptake capacity, lactic acid content, ECAR and HK2 expression were detected in LC cells subjected to GA treatment or HK2-knockdown. Conversely, overexpression of HK2 reversed these trends, indicating that glycyrrhizin may inhibit LC cell proliferation and the Warburg effect through suppression of HK2. In addition, it was revealed that the PI3K/AKT signaling pathway was associated with LC cell proliferation and the Warburg effect; notably, treatment of LC cells with the AKT agonist SC79 induced elevation of the ECAR, cell proliferation, glucose uptake capacity, lactic acid content, phosphorylated-AKT and HK2 expression, and suppressed the OCR. In conclusion, GA may inhibit the Warburg effect and cell proliferation in LC by suppressing HK2 through blockade of the PI3K/AKT signaling pathway.

show abstract

“…Both the membrane localization and the glucose uptake of GLUT1 play important roles in the Warburg effect. 20 In this study, we have provided evidence that the overexpression of both E6 and E7 in HPV16 down-regulated the expression level of miR-451 in lung cancer cells. However, because the carcinogenesis mechanism of E6 and E7 proteins is not the same, the regulation pathways of miR-451 by both proteins may not be the same.…”

Section: Discussionmentioning

confidence: 69%

HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway via relieving miR-451 inhibitory effect on CAB39 in lung cancer cells

Wang

et al. 2020

Therapeutic Advances in Chronic Disease

View full text Add to dashboard Cite

Background: HPV16 E6/E7 proteins are the main oncogenes and only long-term persistent infection causes lung cancer. Our previous studies have shown that HPV16 E6/E7 protein up-regulates the expression of GLUT1 in lung cancer cells. However, whether E6 and E7 protein can promote the glucose uptake of GLUT1 and its molecular mechanism are unclear. Methods: The regulatory relationships of E6 or E7, miR-451, CAB39, PI3K/AKT, and GLUT1 were detected by double directional genetic manipulations in lung cancer cell lines. Immunofluorescence and flow cytometry were used to detect the effect of CAB39 on promoting the translocation to the plasma membrane of GLUT1. Flow cytometry and confocal microscopy were performed to detect the glucose uptake levels of GLUT1. Results: The overexpression both E6 and E7 proteins significantly down-regulated the expression level of miR-451, and the loss of miR-451 further up-regulated the expression of its target gene CAB39 at both protein and mRNA levels. Subsequently, CAB39 up-regulated the expression of GLUT1 at both protein and mRNA levels. Our results demonstrated that HPV16 E6/E7 up-regulated the expression and activation of GLUT1 through the HPV–miR-451–CAB39–GLUT1 axis. More interestingly, we found that CAB39 prompted GLUT1 translocation to the plasma membrane and glucose uptake, and this promotion depended on the PI3K/AKT pathway. Conclusion: Our findings provide new evidence to support the critical roles of miR-451 and CAB39 in the pathogenesis of HPV-related lung cancer.

show abstract

Mitochondrial miR-181a-5p promotes glucose metabolism reprogramming in liver cancer by regulating the electron transport chain

Cited by 45 publications

References 45 publications

RNA-sequencing of peripheral blood circular RNAs in Parkinson disease

RNA-sequencing of peripheral blood circular RNAs in Parkinson disease

HK2 is associated with the Warburg effect and proliferation in liver cancer: Targets for effective therapy with glycyrrhizin

HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway via relieving miR-451 inhibitory effect on CAB39 in lung cancer cells

Contact Info

Product

Resources

About