Zinc and p53 disrupt mitochondrial binding of HK2 by phosphorylating VDAC1

Xue, Yanan; Yu, Bingbing; Li, Jiu-Ling; Guo, Rui; Zhang, Lichao; Sun, Liankun; Liu, Yanan; Li, Yang

doi:10.1016/j.yexcr.2018.12.002

Cited by 23 publications

(19 citation statements)

References 43 publications

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“…Voltage-dependent anion channel 1 (VDAC1) is an important regulator of mPTP opening. HK2 interacts with VDAC1 to change the conformation of VDAC1, which leads to an inhibition of mPTP opening [48][49][50]. This correlates with our discovery that silencing HK2, the target of miR-22, aggravates TGEV-induced mPTP opening.…”

Section: Discussionsupporting

confidence: 83%

Circular RNA CircEZH2 Suppresses Transmissible Gastroenteritis Coronavirus-induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR-22 in IPEC-J2

Zhao¹,

Ma²,

Guo³

et al. 2019

Int. J. Biol. Sci.

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Transmissible gastroenteritis (TGE) is a contagious and infectious disease that is characterized by severe vomiting and diarrhea of swine , especially piglet, and caused by transmissible gastroenteritis coronavirus (TGEV) . TGEV infection provokes mitochondrial damage of porcine intestinal epthelial cell (IPEC), which is responsible for inflammation and cell death. In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2). Activation of NF-κB is an important factor for mitochondrial damage. Mitochondrial permeability transition pore (mPTP) opening is a key reason for mitochondrial damage. So, we speculate that circEZH2 may regulate TGEV-induced mPTP opening via NF-kB pathway. In the present study, we found that mPTP opening of IPEC-J2 was occured during TGEV infection and suppressed by circEZH2 via attaching miR-22. Hexokinase 2 (HK2) and interleukin 6 (IL-6) were identified as the targets of miR-22. Silencing HK2 enhanced TGEV-induced mPTP opening, while no effect on NF-κB pathway. Silencing IL-6 promoted TGEV-induced mPTP opening and inhibited NF-κB pathway. Inhibitor of NF-κB increased TGEV-induced mPTP opening. The data revealed that TGEV-induced mPTP opening was regulated via two pathways: circEZH2/miR-22/HK2 axis and circEZH2/miR-22/IL-6/NF-κB axis.

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Section: Discussionsupporting

confidence: 83%

Circular RNA CircEZH2 Suppresses Transmissible Gastroenteritis Coronavirus-induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR-22 in IPEC-J2

Zhao¹,

Ma²,

Guo³

et al. 2019

Int. J. Biol. Sci.

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“…Mitochondria-localized HK2 has been shown to be required for escaping from mitochondrial cell death in several types of human cancer [28][29][30][31]. Here, we found that xanthohumol suppressed HK2 expression and induced the activation of mitochondrial apoptosis signaling.…”

Section: Discussionmentioning

confidence: 63%

Xanthohumol inhibits colorectal cancer cells via downregulation of Hexokinases II-mediated glycolysis

Liu¹,

Li²,

Liu³

et al. 2019

Int. J. Biol. Sci.

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Deregulation of glycolysis is a common phenomenon in human colorectal cancer (CRC). In the present study, we reported that Hexokinase 2 (HK2) is overexpressed in human CRC tissues and cell lines, knockout of HK2 inhibited cell proliferation, colony formation, and xenograft tumor growth. We demonstrated that the natural compound, xanthohumol, has a profound anti-tumor effect on CRC via down-regulation of HK2 and glycolysis. Xanthohumol suppressed CRC cell growth both in vitro and in vivo. Treatment with xanthohumol promoted the release of cytochrome C and activated the intrinsic apoptosis pathway. Moreover, our results revealed that xanthohumol down-regulated the EGFR-Akt signaling, exogenous overexpression of constitutively activated Akt1 significantly impaired xanthohumol-induced glycolysis suppression and apoptosis induction. Our results suggest that targeting HK2 appears to be a new approach for clinical CRC prevention or treatment.

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“…In previous sections, we dealt with the anito‐apoptotic role of hexokinase 2. Therefore, it is possible that phachymic acid may be able to induce apoptosis through mechanisms such as separating HK2 from the mitochondrial membrane (Miao et al, 2019; Xue et al, 2019). In addition, phachymic acid can increase the expression of PTEN and attenuate AKT/PI3K signaling pathway in cancer cells (Wen et al, 2018).…”

Section: Metabolism As Target For Cancer Treatmentmentioning

confidence: 99%

Signaling, metabolism, and cancer: An important relationship for therapeutic intervention

Vaghari‐Tabari

Qujeq

Andevari

et al. 2021

Journal Cellular Physiology

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In cancerous cells, significant changes occur in the activity of signaling pathways affecting a wide range of cellular activities ranging from growth and proliferation to apoptosis, invasiveness, and metastasis. Extensive changes also happen with respect to the metabolism of a cancerous cell encompassing a wide range of functions that include: nutrient acquisition, biosynthesis of macromolecules, and energy generation. These changes are important and some therapeutic approaches for treating cancers have focused on targeting the metabolism of cancerous cells. Oncogenes and tumor suppressor genes have a significant effect on the metabolism of cells. There appears to be a close interaction between metabolism and the signaling pathways in a cancerous cell, in which the interaction provides the metabolic needs of a cancerous cell for uncontrolled proliferation, resistance to apoptosis, and metastasis. In this review, we have reviewed the latest findings in this regard and briefly review the most recent research findings regarding targeting the metabolism of cancer cells as a therapeutic approach for treatment of cancer.

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Zinc and p53 disrupt mitochondrial binding of HK2 by phosphorylating VDAC1

Cited by 23 publications

References 43 publications

Circular RNA CircEZH2 Suppresses Transmissible Gastroenteritis Coronavirus-induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR-22 in IPEC-J2

Circular RNA CircEZH2 Suppresses Transmissible Gastroenteritis Coronavirus-induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR-22 in IPEC-J2

Xanthohumol inhibits colorectal cancer cells via downregulation of Hexokinases II-mediated glycolysis

Signaling, metabolism, and cancer: An important relationship for therapeutic intervention

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