Involvement of riboflavin kinase expression in cellular sensitivity against cisplatin

Hirano, Gen; Izumi, Hiroto; Yasuniwa, Yoshihiro; Shimajiri, Shohei; Wang, Ke-Yong; Sasagiri, Yasuyuki; Kusaba, Hitoshi; Matsumoto, Kaori; Hasegawa, Tetsuya; Akimoto, Masayuki; Akashi, Koichi; Kohno, Kimitoshi

doi:10.3892/ijo.2011.938

Cited by 14 publications

(9 citation statements)

References 25 publications

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“…We confirmed that another highly edited intestinal Apobec-1-dependent target, Cd36, also showed concordant decreases in RNA and protein abundance in Apobec-1 null mice. The functional implications of these changes will require formal confirmation but targets including Rfk, Tes, Pde5a, Yme1l1 and Ido1 have been implicated in tumorigenesis [ 30 - 35 ]. This possibility is intriguing in view of findings that Apobec-1 deletion attenuates the tumor burden in Apc Min/+ mice [ 36 ] while deficiency of Deadend1 ( Dnd1 ), a paralog of ACF, increases intestinal polyposis susceptibility in Apc Min/+ mice [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U RNA editing in mouse small intestine and liver

et al. 2014

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BackgroundRNA editing encompasses a post-transcriptional process in which the genomically templated sequence is enzymatically altered and introduces a modified base into the edited transcript. Mammalian C-to-U RNA editing represents a distinct subtype of base modification, whose prototype is intestinal apolipoprotein B mRNA, mediated by the catalytic deaminase Apobec-1. However, the genome-wide identification, tissue-specificity and functional implications of Apobec-1-mediated C-to-U RNA editing remain incompletely explored.ResultsDeep sequencing, data filtering and Sanger-sequence validation of intestinal and hepatic RNA from wild-type and Apobec-1-deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs, all within 3′ untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites are unique to liver. Changes in RNA editing lead to corresponding changes in intestinal mRNA and protein levels for 11 genes. Analysis of RNA editing in vivo following tissue-specific Apobec-1 adenoviral or transgenic Apobec-1 overexpression reveals that a subset of targets identified in wild-type mice are restored in Apobec-1-deficient mouse intestine and liver following Apobec-1 rescue. We find distinctive polysome profiles for several RNA editing targets and demonstrate novel exonic editing sites in nuclear preparations from intestine but not hepatic apolipoprotein B RNA. RNA editing is validated using cell-free extracts from wild-type but not Apobec-1-deficient mice, demonstrating that Apobec-1 is required.ConclusionsThese studies define selective, tissue-specific targets of Apobec-1-dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific.

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Section: Discussionmentioning

confidence: 99%

Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U RNA editing in mouse small intestine and liver

et al. 2014

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“…The sensitive cells were unresponsive to induction at all concentrations of CA unlike the resistant cells in which 50 µM CA induced a 6-fold overexpression. Hirano et al, found that overexpression of riboflavin kinase which is involved in the first step in the FAD synthesis (FAD is an essential co enzyme for GSR) renders cell resistance not only to cisplatin but also to hydrogen peroxide [49] . Cisplatin induces oxidative stress and hydrogen peroxide production in cells and is believed to be one of the mechanisms underlying cisplatin-induced nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

The role of the catecholic and the electrophilic moieties of caffeic acid in Nrf2/Keap1 pathway activation in ovarian carcinoma cell lines

2015

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In recent years, numerous studies have demonstrated the health benefits of polyphenols. A major portion of polyphenols in western diet are derived from coffee, which is one of the most consumed beverages in the world.It has been shown that many polyphenols gain their beneficial properties (e.g. cancer prevention) through the activation of the Nrf2/Keap1 pathway as well as their direct antioxidant activity. However, activation of Nrf2 in cancer cells might lead to resistance towards therapy through induction of phase II enzymes.In the present work we hypothesize that caffeic acid (CA), a coffee polyphenol, might act as an electrophile in addition to its nucleophilic properties and is capable of inducing the Nrf2/EpRE pathway in cancer cells.The results indicate that CA induces Nrf2 translocation into the nucleus and consequently its transcription. It has been demonstrated that generated hydrogen peroxide is involved in the induction process. It has also been found that this process is induced predominantly via the double bond in CA (Michael acceptor). However, surprisingly the presence of both nucleophilic and electrophilic moieties in CA resulted in a synergetic activation of Nrf2 and phase II enzymes.We also found that CA possesses a dual activity, although inducing GSTP1 and GSR, it inhibiting their enzymatic activity.In conclusion, the mechanism of induction of Nrf2 pathway and phase II enzymes by CA has been elucidated. The electrophilic moiety in CA is essential for the oxidation of the Keap1 protein. It should be noted that while the nucleophilic moiety (the catechol/quinone moiety) can provide scavenging ability, it cannot contribute directly to Nrf2 induction. It was found that this process may be induced by H2O2 produced by the catechol group.On the whole, it appears that CA might play a major role in the cancer cells by enhancing their resistance to treatment.

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“…Clusterin, a chaperone protein upexpressed in prostate cancer, stabilizes Ku70/BAX complexes, sequestering BAX from its ability to induce mitochondrial release of cytochrome c , thus avoiding subsequent apoptosis and promoting resistance to cisplatin; the secreted clusterin form is expressed in aggressive late stage tumours, and although its high expression may be considered an adaptive response to OS, it enhances the survival potential of cancerous cells [ 195 ]. Overexpression of riboflavin kinase, necessary for synthesis of FAD and glutathione reduction, is upregulated in cisplatin-resistant cells and it is related to prostate cancer progression [ 196 ]. The ubiquitin-specific protease 2a (USP2A), a deubiquitinating enzyme overexpressed in prostate adenocarcinomas, confers resistance to cisplatin; USP2A increases intracellular reduced glutathione content, reduces ROS production, and impairs the activation of apoptosis [ 197 ].…”

Section: Cisplatin Chemoresistance Oxidative Stress and Hmgb Prmentioning

confidence: 99%

High Mobility Group B Proteins, Their Partners, and Other Redox Sensors in Ovarian and Prostate Cancer

Barreiro-Alonso¹,

Lamas-Maceiras²,

Rodrı́guez-Belmonte³

et al. 2015

Oxidative Medicine and Cellular Longevity

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Cancer cells try to avoid the overproduction of reactive oxygen species by metabolic rearrangements. These cells also develop specific strategies to increase ROS resistance and to express the enzymatic activities necessary for ROS detoxification. Oxidative stress produces DNA damage and also induces responses, which could help the cell to restore the initial equilibrium. But if this is not possible, oxidative stress finally activates signals that will lead to cell death. High mobility group B (HMGB) proteins have been previously related to the onset and progressions of cancers of different origins. The protein HMGB1 behaves as a redox sensor and its structural changes, which are conditioned by the oxidative environment, are associated with different functions of the protein. This review describes recent advances in the role of human HMGB proteins and other proteins interacting with them, in cancerous processes related to oxidative stress, with special reference to ovarian and prostate cancer. Their participation in the molecular mechanisms of resistance to cisplatin, a drug commonly used in chemotherapy, is also revised.

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Involvement of riboflavin kinase expression in cellular sensitivity against cisplatin

Cited by 14 publications

References 25 publications

Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U RNA editing in mouse small intestine and liver

Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U RNA editing in mouse small intestine and liver

The role of the catecholic and the electrophilic moieties of caffeic acid in Nrf2/Keap1 pathway activation in ovarian carcinoma cell lines

High Mobility Group B Proteins, Their Partners, and Other Redox Sensors in Ovarian and Prostate Cancer

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