High Expression of Aldo-Keto Reductase 1B10 Is an Independent Predictor of Favorable Prognosis in Patients with Hepatocellular Carcinoma

Ha, Sang Yun; Song, Dae Hyun; Lee, Jae Jun; Lee, Hyun Woo; Cho, Soo Youn; Park, Cheol-Keun

doi:10.5009/gnl13406

Cited by 29 publications

(39 citation statements)

References 23 publications

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“…Silencing of AKR1B10 with siRNA suppresses HCC tumor growth [ 30 ]. Although the expression of AKR1B10 is increased in primary HCC tumors, several studies indicate that AKR1B10 is paradoxically correlated with the less aggressive and well-differentiated HCC tumors [ 23 , 31 – 33 ]. These results suggest that decreased expression of AKR1B10 is associated with the more advanced and malignant HCC.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Aldo-keto-reductase family 1 B10 by 14-3-3ε and their prognostic impact of hepatocellular carcinoma

Liu

Jan

et al. 2015

Oncotarget

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14-3-3ε is overexpressed in hepatocellular carcinoma (HCC) and its expression significantly associates with a poor prognostic outcome. To uncover how 14-3-3ε contributes to the tumor progression of HCC, we investigated the potential downstream targets regulated by 14-3-3ε. We found that 14-3-3ε increases expression and nuclear translocation of β-catenin and that 14-3-3ε-induced cell proliferation is attenuated by β-catenin silencing in HCC cells. Moreover, 14-3-3ε induces aldo-keto reductase family 1 member B10 (AKR1B10) expression through the activation of β-catenin signaling. Knockdown of AKR1B10 by siRNAs abolished 14-3-3ε-induced in vitro cell proliferation, anchorage-independent growth as well as in vivo tumor growth. Furthermore, AKR1B10 silencing increased retinoic acid (RA) levels in the serum of tumor-bearing mice and RA treatment attenuated 14-3-3ε-induced HCC cell proliferation. We further examined 14-3-3ε and AKR1B10 expression and clinicopathological characteristics of HCC tumors. Although the expression of AKR1B10 was significantly correlated with 14-3-3ε, an increase of AKR1B10 expression in 14-3-3ε positive patients paradoxically had better overall survival and disease-free survival rates as well as lower metastatic incidence than those without an AKR1B10 increase. Finally, we found a loss of AKR1B10 expression in cells exhibiting a high capacity of invasiveness. Silencing of AKR1B10 resulted in inducing snail and vimentin expression in HCC cells. These results indicate that AKR1B10 may play a dual role during HCC tumor progression. Our results also indicate that 14-3-3ε regulates AKR1B10 expression by activating β-catenin signaling. A combination of 14-3-3ε with AKR1B10 is a potential therapeutic target and novel prognostic biomarker of HCC.

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Section: Introductionmentioning

confidence: 99%

Regulation of Aldo-keto-reductase family 1 B10 by 14-3-3ε and their prognostic impact of hepatocellular carcinoma

Liu

Jan

et al. 2015

Oncotarget

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“…After full-text review, 12 articles were excluded. Eventually, we identi ed 11 articles published between 2014 and 2019, which were included in the nal analysis [5][6][7][8][9][10][11][12][13][14][15]. The ow diagram of the literature search is shown in Fig1.…”

Section: Study Selectionmentioning

confidence: 99%

“…Studies have shown that AKR1B10 is characterized by obvious carcinogenicity and can be used as a tumor marker [4]. Recently, an increasing number of studies showed that abnormal expression of AKR1B10 is signi cantly correlated with the prognosis of certain solid tumors [5][6][7][8][9][10][11][12][13][14][15]. However, the currently available results are inconsistent, and the prognostic value of AKR1B10 remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of aldo-keto reductase family 1 member B10 in solid tumors: a systematic review and meta-analysis

Liu

Zheng

Peng

et al. 2020

Preprint

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Background: It has been reported that the expression of aldo-keto reductase family 1 member B10 (AKR1B10) is abnormal in various types of cancer, and could be used as a prognostic biomarker. However, the results are controversial. Therefore, the aim of this study was to comprehensively evaluate the prognostic value of AKR1B10 expression in solid tumors by conducting a meta-analysis.Methods: The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival and disease-free survival/relapse-free survival were calculated to estimate the prognostic significance of AKR1B10 using the random effects model. Subgroup, meta-regression, and sensitivity analyses were used to investigate sources of heterogeneity. Begg’s test and Egger’s test were used to evaluate publication bias.Results: Eleven studies involving 1,389 patients were included in this meta-analysis. The pooled analysis displayed that high expression of AKR1B10 was not associated with OS(HR=1.22; 95% CI: 0.73–2.04) and DFS/PFS (HR=1.23, 95% CI 0.75–2.01) in solid tumors. Sensitivity analysis indicated that the results of the meta-analysis were stable. Begg’s test and Egger’s test also confirmed the absence of publication bias.Conclusions: We demonstrated that high expression of AKR1B10 was not associated with survival outcomes in patients with solid tumors. Further large-sample, prospective, multi-centric, and well-designed studies are warranted to investigate the prognostic role of AKR1B10 in various cancers.

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“…These reports collectively emphasize that AKR1 isozymes such as AKR1B10 and AKR1B8 may play a vital role in modulating the development of ulcerative colitis and colitis-associated colorectal cancer in mammals. However, the mechanisms underlying AKR1B10 overexpression in many non-digestive tract cancers [12,13,15,18] are still not well elucidated, therefore efforts are needed to discover the relationship between AKR1B10 overexpression and cancer formation.…”

Section: Akr1b10 In Cancer Formationmentioning

confidence: 99%

“…On the contrary, the expression of AKR1B10 is downregulated in gastrointestinal cancer [16,17]. AKR1B10 overexpression has been considered as a valuable biomarker and prognostic indicator for some cancers [15,17,18], and low expression of AKR1B10 has been used as a biomarker for the diagnosis of bowel diseases (US8551720) [19]. AKR1B10 is a protein secreted through a lysosome-mediated pathway and may serve as a potential serum marker for malignant diseases [20].…”

Section: Introductionmentioning

confidence: 99%

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

Li¹,

He²,

Luo³

et al. 2016

PRA

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Cytosolic NADPH-dependent reductase AKR1B10 is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is normally expressed in the gastrointestinal tract. However, it is overexpressed in many solid tumors, such as hepatocarcinoma, lung cancer and breast cancer. AKR1B10 may play a role in the formation and development of carcinomas through multiple mechanisms including detoxification of cytotoxic carbonyls, modulation of retinoic acid level, and regulation of cellular fatty acid synthesis and lipid metabolism. Studies have suggested that AKR1B10 may be a useful biomarker for cancer diagnosis and a potential target for cancer treatment. Over the last decade, a number of AKR1B10 inhibitors including aldose reductase inhibitors (ARIs), endogenous substances, natural-based derivatives and synthetic compounds have been developed, which could be novel anticancer drugs. This review provides an overview on related articles and patents about AKR1B10 inhibitors, with a focus on their inhibition selectivity and mechanism of function.

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High Expression of Aldo-Keto Reductase 1B10 Is an Independent Predictor of Favorable Prognosis in Patients with Hepatocellular Carcinoma

Cited by 29 publications

References 23 publications

Regulation of Aldo-keto-reductase family 1 B10 by 14-3-3ε and their prognostic impact of hepatocellular carcinoma

Regulation of Aldo-keto-reductase family 1 B10 by 14-3-3ε and their prognostic impact of hepatocellular carcinoma

Prognostic value of aldo-keto reductase family 1 member B10 in solid tumors: a systematic review and meta-analysis

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

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