A PINK1-mediated mitophagy pathway decides the fate of tumors—to be benign or malignant?

Qian, Hui; Chao, Xiaojuan; Ding, Wen–Xing

doi:10.1080/15548627.2018.1425057

Cited by 14 publications

(8 citation statements)

References 16 publications

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“…Sp1 can promote the expression of its target genes [42]. Generally, the level of gene transcription in eukaryotic cells is dependent on the binding of RNA polymerase and transcription factors to specific sequences in gene promoters [43]. Sp1 functions by interacting with the TATA-box binding protein complex (TFIID) and facilitating binding of TFIID to the promoter, which, in turn, recruits RNA polymerase II (Pol II) [29,44].…”

Section: Discussionmentioning

confidence: 99%

Sp1 is Involved in Vertebrate LC-PUFA Biosynthesis by Upregulating the Expression of Liver Desaturase and Elongase Genes

Zhao

Dong

et al. 2019

IJMS

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The rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the ability for the biosynthesis of long-chain (≥C20) polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors, and all the catalytic enzymes including two fatty acyl desaturase 2 (Δ4 Fads2 and Δ6/Δ5 Fads2) and two elongases (Elovl4 and Elovl5) have been identified, providing a good model for studying the regulatory mechanisms of LC-PUFA biosynthesis in fish. Stimulatory protein 1 (Sp1) has been speculated to be a vital transcription factor in determining the promoter activity of Fads-like genes in fish, however its regulatory effects on gene expression and LC-PUFA biosynthesis have not been demonstrated. Bioinformatic analysis predicted potential Sp1 binding sites in the promoters of the rabbitfish Δ6/Δ5 fads2 and elovl5, but not in Δ4 fads2 promoter. Here we cloned full-length cDNA of the rabbitfish sp1 gene, which encoded a putative protein of 701 amino acids, and was expressed in all tissues studied with highest levels in gill and eyes. The dual luciferase reporter assay in HepG2 line cells demonstrated the importance of the Sp1 binding site for the promoter activities of both Δ6/Δ5 fads2 and elovl5. Moreover, the electrophoretic mobility shift assay confirmed the direct interaction of Sp1 with the two promoters. Insertion of the Sp1 binding site of Δ6/Δ5 fads2 promoter into the corresponding region of the Δ4 fads2 promoter significantly increased activity of the latter. In the Siganus canaliculatus hepatocyte line (SCHL) cells, mRNA levels of Δ6/Δ5 fads2 and elovl5 were positively correlated with the expression of sp1 when sp1 was overexpressed or knocked-down by RNAi or antagonist (mithramycin) treatment. Moreover, overexpression of sp1 also led to a higher conversion of 18:2n−6 to 18:3n−6, 18:2n−6 to 20:2n−6, and 18:3n−3 to 20:3n−3, which related to the functions of Δ6/Δ5 Fads2 and Elovl5, respectively. These results indicated that Sp1 is involved in the transcriptional regulation of LC-PUFA biosynthesis by directly targeting Δ6/Δ5 fads2 and elovl5 in rabbitfish, which is the first report of Sp1 involvement in the regulation of LC-PUFA biosynthesis in vertebrates.

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Section: Discussionmentioning

confidence: 99%

Sp1 is Involved in Vertebrate LC-PUFA Biosynthesis by Upregulating the Expression of Liver Desaturase and Elongase Genes

Zhao

Dong

et al. 2019

IJMS

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“…When mitophagy is impaired, PINK1-activated p53 can translocate to the nucleus, which would otherwise be degraded by mitophagy, to suppress the expression of NANOG, a key transcription factor required for stem cell self-renewal, resulting in a reduced CSC population [220]. These findings suggest that mitophagy can sustain tumor cell metabolism and provide them with nutrients for tumor growth and survival, which is required for malignant tumor progression [221]. Overall, similar to general autophagy, it seems that mitophagy also plays a dual role in liver cancer development depending on the stage of tumorigenesis.…”

Section: Mitophagy In Liver Cancermentioning

confidence: 99%

Role and Mechanisms of Mitophagy in Liver Diseases

McKeen

Zhang

et al. 2020

Cells

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169

122

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The mitochondrion is an organelle that plays a vital role in the regulation of hepatic cellular redox, lipid metabolism, and cell death. Mitochondrial dysfunction is associated with both acute and chronic liver diseases with emerging evidence indicating that mitophagy, a selective form of autophagy for damaged/excessive mitochondria, plays a key role in the liver’s physiology and pathophysiology. This review will focus on mitochondrial dynamics, mitophagy regulation, and their roles in various liver diseases (alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, and cancer) with the hope that a better understanding of the molecular events and signaling pathways in mitophagy regulation will help identify promising targets for the future treatment of liver diseases.

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“…14 Based on accumulating evidence, it has been established that imbalanced mitophagy plays a dual role in the neoplastic progression and drug resistance of different tumor types. 15,16 Both the inhibition and induction of mitophagy have been reported to enhance the drug sensitivity of different tumor cells. 17 ZnO NPs significantly induce autophagy in human ovarian cancer cells by inducing reactive oxygen species (ROS) production.…”

Section: Introductionmentioning

confidence: 99%

Zinc oxide nanoparticles induce toxicity in CAL 27 oral cancer cell lines by activating PINK1/Parkin-mediated mitophagy

Wang¹,

Gao²,

Wang³

et al. 2018

IJN

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BackgroundTongue squamous cell carcinoma (tongue cancer) is one of the most common malignancies in the oral maxillofacial region. The tumor easily relapses after surgery, and the prognosis remains poor. Recently, zinc oxide nanoparticles (ZnO NPs) were shown to target multiple cancer cell types. In this study, we aimed to elucidate the anticancer effect of ZnO NPs on CAL 27 human tongue cancer cells and identify the role of PINK1/Parkin-mediated mitophagy in this effect.Materials and methodsWe analyzed the dose-dependent cytotoxic effects of ZnO NPs on CAL 27 cells. Cells were cultured in media containing 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 μg/mL ZnO NPs for 24 h. We further examined the intracellular reactive oxygen species levels, monodansylcadaverine intensity and mitochondrial membrane potential following the administration of 25 μg/mL ZnO NPs for 4, 8, 12, or 24 h and investigated the role of PINK1/Parkin-mediated mitophagy in ZnO NP-induced toxicity in CAL 27 cells.ResultsThe viability of CAL 27 cells decreased after treatment with increasing ZnO NP concentrations. The inhibitory concentration 50% of the ZnO NPs was calculated as 25 μg/mL. The ZnO NPs increased the intracellular reactive oxygen species levels and decreased the mitochondrial membrane potential in a time-dependent manner as well as activated the PINK1/Parkin-mediated mitophagy process in CAL 27 cells.ConclusionBased on our findings, ZnO NPs may possess potential anticancer activity toward tongue cancer cells.

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A PINK1-mediated mitophagy pathway decides the fate of tumors—to be benign or malignant?

Cited by 14 publications

References 16 publications

Sp1 is Involved in Vertebrate LC-PUFA Biosynthesis by Upregulating the Expression of Liver Desaturase and Elongase Genes

Sp1 is Involved in Vertebrate LC-PUFA Biosynthesis by Upregulating the Expression of Liver Desaturase and Elongase Genes

Role and Mechanisms of Mitophagy in Liver Diseases

Zinc oxide nanoparticles induce toxicity in CAL 27 oral cancer cell lines by activating PINK1/Parkin-mediated mitophagy

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