Downregulation of AKR1B10 expression in colorectal cancer

Kropotova, Ekaterina S.; Tychko, R. A.; Zinov’eva, O. L.; Zyryanova, Alisa; Khankin, S. L.; Cherkes, V L; Алиев, В. А.; Beresten, S. F.; Oparina, N. Yu.; Mashkova, T. D.

doi:10.1134/s0026893310020056

Cited by 29 publications

(22 citation statements)

References 33 publications

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“…AKR1B10 is primarily expressed in the colon and small intestine , but downregulated in colorectal cancer . Consistently, this study found that AKR1B10 expression decreased in colorectal cancer at both mRNA and protein levels (Figure A).…”

Section: Resultssupporting

confidence: 85%

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Aldo-keto reductase 1B10 protects human colon cells from DNA damage induced by electrophilic carbonyl compounds

Yan

Pan

et al. 2016

Mol. Carcinog.

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Electrophilic carbonyl compounds are highly cytotoxic and genotoxic. Aldo-keto reductase 1B10 (AKR1B10) is an enzyme catalyzing reduction of carbonyl compounds to less toxic alcoholic forms. This study presents novel evidence that AKR1B10 protects colon cells from DNA damage induced by electrophilic carbonyl compounds. AKR1B10 is specifically expressed in epithelial cells of the human colon, but this study found that AKR1B10 expression was lost or markedly diminished in colorectal cancer, precancerous tissues, and a notable portion of normal adjacent tissues (NAT). SiRNA-mediated silencing of AKR1B10 in colon cancer cells HCT-8 enhanced cytotoxicity of acrolein and HNE, whereas ectopic expression of AKR1B10 in colon cancer cells RKO prevented the host cells against carbonyl cytotoxicity. Furthermore, siRNA-mediated AKR1B10 silencing led to DNA breaks and activation of γ-H2AX protein, a marker of DNA double strand breaks, particularly in the exposure of HNE (10 μM). In the AKR1B10 silenced HCT-8 cells, hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutant frequency increased by 26.8 times at basal level and by 33.5 times in the presence of 10 μM HNE when compared to vector control cells. In these cells, the cyclic acrolein-deoxyguanosine adducts levels were increased by over 10 times. These findings were confirmed by pharmacological inhibition of AKR1B10 activity by Epalrestat. Taken together, these data suggest that AKR1B10 is a critical protein that protects host cells from DNA damage induced by electrophilic carbonyl compounds. AKR1B10 deficiency in the colon may be an important pathogenic factor in disease progression and carcinogenesis. © 2016 Wiley Periodicals, Inc.

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Section: Resultssupporting

confidence: 85%

“…AKR1B10 is primarily expressed in intestinal epithelial cells , but downregulated in colorectal cancer . The downregulation of AKR1B10 may inhibit p53‐induced apoptosis and disrupt homeostasis of retinoic acid, promoting progression of colorectal carcinoma .…”

Section: Discussionmentioning

confidence: 99%

Aldo-keto reductase 1B10 protects human colon cells from DNA damage induced by electrophilic carbonyl compounds

Yan

Pan

et al. 2016

Mol. Carcinog.

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“…In fact, downregulated AKR1B10 levels are seen in nearly 88% of colorectal carcinomas. 8 Simultaneous attenuation of AKR1B1 is seen in 10% of colorectal carcinomas. Bortezomib causes upregulation of AKR1B10, and this finding may explain its potential chemotherapeutic role in colorectal carcinomas.…”

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confidence: 99%

AKR1B10 and its emerging role in tumor carcinogenesis and as a cancer biomarker

Kapoor¹

2012

Intl Journal of Cancer

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I read with great interest the recent article by Ma et al. in a recent issue of your esteemed journal.1 The article is highly thought provoking. Interestingly, new data have recently emerged over the past few years that implicate AKR1B10 in tumor carcinogenesis in different systemic malignancies besides breast carcinomas.For instance, increased expression of AKR1B10 is seen in nearly 84% of squamous cell pulmonary carcinomas.2 In fact, a close co-relation exists between AKR1B10 expression by lung cancers and smoking habits.3 AKR1B10 is therefore rapidly emerging as a sensitive marker of nonsmall cell lung carcinomas especially in smokers. 4 Similarly, AKR1B10 alters prenylation of pancreatic proteins. As a result, tumor carcinogenesis is accentuated in pancreatic carcinomas. In fact, 70% of pancreatic adenocarcinomas demonstrate increased AKR1B10 expression, thus making AKR1B10 a potential biomarker of pancreatic malignancies. 5AKR1B10 is also emerging as a prognostic biomarker of hepatocellular carcinomas. For instance, a better prognostic outcome is seen with accentuated AKR1B10 expression. 6Increased AKR1B10 expression is especially associated with underlying cirrhosis and viral-mediated hepatocellular carcinomas. AKR1B10 expression also serves as a prognostic biomarker of bladder carcinogenesis. For instance, postcystectomy patients who receive dual gemcitabine and carboplatin therapy and express AKR1B10 generally tend to have a poor clinical outcome.7 Attenuated AKR1B10 expression in colonic tissue also serves as a marker of carcinogenesis in these tissues. In fact, downregulated AKR1B10 levels are seen in nearly 88% of colorectal carcinomas.8 Simultaneous attenuation of AKR1B1 is seen in 10% of colorectal carcinomas. Bortezomib causes upregulation of AKR1B10, and this finding may explain its potential chemotherapeutic role in colorectal carcinomas. 9The above examples clearly illustrate the role of AKR1B10 in tumor carcinogenesis and the need for further large-scale studies to fully elaborate its role and prognostic significance in other tumors.

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“…AKR1B10 is primarily expressed in the human colon and small intestine, which efficiently catalyzes the reduction of aromatic and aliphatic aldehydes and dicarbonyl compounds, and regulates cell survival and growth by modulating the synthesis of lipid and the membrane function . Comparing within normal colon tissues, the expression of AKR1B10 is significantly decreased in colorectal cancers and adenomas (Kropotova et al 2010;Martin and Maser 2009). Therefore, AKR1B10 is recognized as a novel prognostic predictor and therapeutic target for colorectal cancer (Díez-Dacal et al 2011;Laffin and Petrash 2012).…”

Section: Introductionmentioning

confidence: 99%

Facile fabrication of CdSe/CdS quantum dots and their application on the screening of colorectal cancer

Cao

Dong

et al. 2015

J Nanopart Res

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In this paper, a facile aqueous route to water-soluble CdSe/CdS quantum dots (QDs) under mild conditions has been developed. The samples were characterized by means of transmission electron microscopy, energy-dispersive X-ray spectroscopy, and photoluminescence (PL) spectroscopy. The PL property of the QDs can be controlled by adjusting the reaction time. The CdSe/CdS QDs after 48-h reaction with size of 5 nm have the strongest PL intensity located at 553 nm, and the highest quantum yield of 19.9 %. The obtained QDs were applied for the colorectal cancer screening. The QDs could be conjugated with antibody of aldo-keto reductase family 1, member B10 (AKR1B10) for the detection of AKR1B10. The AKR1B10 in PBS/5 % serum solution with concentration of 1 ng/mL could be well calibrated, and the limit of detection could be lower than 0.05 ng/mL.Keywords CdSe/CdS quantum dots Á Water soluble Á Colorectal cancer Á Aldo-keto reductase family 1, member B10 (AKR1B10) Á Nanomedicine Á Health effects

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Downregulation of AKR1B10 expression in colorectal cancer

Cited by 29 publications

References 33 publications

Aldo-keto reductase 1B10 protects human colon cells from DNA damage induced by electrophilic carbonyl compounds

Aldo-keto reductase 1B10 protects human colon cells from DNA damage induced by electrophilic carbonyl compounds

AKR1B10 and its emerging role in tumor carcinogenesis and as a cancer biomarker

Facile fabrication of CdSe/CdS quantum dots and their application on the screening of colorectal cancer

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