The role of AKR1 family in tamoxifen resistant invasive lobular breast cancer based on data mining

Xu, Dong; Zhang, Yiqi; Jin, Feng

doi:10.1186/s12885-021-09040-8

Cited by 7 publications

(9 citation statements)

References 43 publications

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“…ERBB4 was downregulated while FN1 was upregulated in TAM-R cells. These findings are supported by previous studies that demonstrated the downregulation of ERBB4 ( 61 ), and the upregulation of FN1 in TAM resistance ( 62 – 64 ). Significant upregulation of VIM, NOTCH1, HES1 , and TP53 in was observed in TAM-R MCF-7 cells, indicating increased Notch signaling, epithelial to mesenchymal transition, and inhibition of cell cycle in TAM-R cells.…”

Section: Discussionsupporting

confidence: 89%

Identification of potential target genes of honokiol in overcoming breast cancer resistance to tamoxifen

et al. 2022

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BackgroundHonokiol (HON) inhibits epidermal growth factor receptor (EGFR) signaling and increases the activity of erlotinib, an EGFR inhibitor, in human head and neck cancers. In this study, using a bioinformatics approach and in vitro experiments, we assessed the target genes of HON against breast cancer resistance to tamoxifen (TAM).Materials and methodsMicroarray data were obtained from GSE67916 and GSE85871 datasets to identify differentially expressed genes (DEGs). DEGs common between HON-treated and TAM-resistant cells were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and protein-protein interaction (PPI) networks were constructed. Selected genes were analyzed for genetic alterations, expression, prognostic value, and receiver operating characteristics (ROC). TAM-resistant MCF-7 (MCF-7 TAM-R) cells were generated and characterized for their resistance toward TAM. A combination of HON and TAM was used for cytotoxicity and gene expression analyses. Molecular docking was performed using the Molecular Operating Environment software.ResultsPPI network analysis revealed that FN1, FGFR2, and RET were the top three genes with the highest scores. A genetic alteration study of potential target genes revealed MMP16 and ERBB4 as the genes with the highest alterations among the breast cancer samples. Pathway enrichment analysis of FGFR2, RET, ERBB4, SOX2, FN1, and MMP16 showed that the genetic alterations herein were likely to impact the RTK-Ras pathway. The expression levels of RET, MMP16, and SOX2 were strongly correlated with prognostic power, with areas under the ROC curves (AUC) of 1, 0.8, and 0.8, respectively. The HON and TAM combination increased TAM cytotoxicity in MCF-7 TAM-R cells by regulating the expression of potential target genes ret, ERBB4, SOX2, and FN1, as well as the TAM resistance regulatory genes including HES1, VIM, PCNA, TP53, and CASP7. Molecular docking results indicated that HON tended to bind RET, ErbB4, and the receptor protein Notch1 ankyrin domain more robustly than its native ligand.ConclusionHON could overcome breast cancer resistance to TAM, potentially by targeting FGFR2, RET, ERBB4, MMP16, FN1, and SOX2. However, further studies are required to validate these results.

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Section: Discussionsupporting

confidence: 89%

Identification of potential target genes of honokiol in overcoming breast cancer resistance to tamoxifen

et al. 2022

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“…In addition, Penning TM et al (2021) noted that these enzymes are involved in the modulation of carcinogen metabolism [35][36][37]. These studies have argued that aldo-keto reductase family 1 members (AKR1s) represent important emerging drug targets that could aid in the development of drugs for the treatment of hormone-dependent forms of cancer such as prostate, hepatocellular, colorectal, breast, and endometrial cancers as well as other diseases [10,14,[38][39][40].…”

Section: Discussionmentioning

confidence: 99%

“…Kamps R. et al claimed that gene expression-based diagnosis, as a new detection method, has diverse application potential in tumour identi cation, tumour monitoring, treatment plan optimization, and improving patient prognosis [12]. Previous studies have established that the expression pro les of AKR1s are an essential component in tumour identi cation and gene expression-based diagnosis [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive clinical analysis of AKR1 expression profiles in the diagnosis of human colorectal cancer

Duan

et al. 2023

Preprint

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Background: CRC has a high mortality rate, and early detection is essential to reducing the CRC-related mortality rate. Screening is inefficient for diagnosis based on the low detection rate, length of time consumed, and poor compliance, so more sensitive and effective diagnostic markers are needed to improve diagnostic efficiency. Aldo-keto reductase family-1 enzymes (AKR1s) play a crucial role in the NADPH-dependent reduction of various carbonyl substrates (aldehyde, ketone), and their expression is closely linked with the progression and invasion of malignant cancers. However, the expression patterns of AKR1 family members in colorectal cancer (CRC) and their unique roles in the diagnosis of CRC have not been explored. Here, the mRNA and protein expression levels of 10 AKR1s and their unique roles in diagnosis in CRC were clarified. Methods: We examined the transcription, methylation and survival data of AKR1s in CRC patients from the Oncomine, Gene Expression Profile Interactive Analysis (GEPIA), Kaplan‒Meier Plotter, cBioPortal and Illumina databases. Then, the mRNA and protein expression levels in CRC tissues were assessed by qRT‒PCR and Western blotting. Results: This study showed that the transcript and protein expression levels of AKR1B1, AKR1B10, AKR1B15, AKR1C1, and AKR1C2 were decreased in CRC tissues compared with adjacentnormal tissues. In contrast, the expression levels of AKR1A1 and AKR1C4 were increased in CRC tissues compared with normal tissues. These expression trends were mostly consistent with those for the Oncomine, GEPIA, TCGA and cBioPortal database analyses, and AKR1B1, AKR1C1 and AKR1C2 were significantly downregulated based in their high CpG methylation levels. The qRT–PCR analysis of AKR1 expression in CRC patients with different clinicopathological characteristics showed that the AKR1A1 expression level was related to invasion depth, and the AKR1C2 expression level was significantly related to TNM stage and distant metastasis. The GEPIA results showed that the malignant degree increased with the increase of AKR1C1, AKR1C2 and AKR1C4 concentration, but the opposite was true for AKR1A1, and ROC curve analysis showed that a low level of AKR1B10 and a high level of AKR1C4 had high diagnostic efficacy in the diagnosis of CRC, with sensitivity values of 71.8% and 70.4% and specificity values of 93.0% and 79.6%, respectively. Conclusion: In summary, the study revealed that AKR1A1 and AKR1C4 have good diagnostic value for CRC and could become potential tumour biomarkers. AKR1B1, AKR1B10 and AKR1B15 may be favourable prognostic indicators.

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“…The contribution of 5Red3 to DHT synthesis and the clinical significance of 5Red3 in breast cancer are largely unclear. However, a recent database analysis showed that overexpression of 5Red3 correlates with lymph node metastasis and shorter overall survival of breast cancer patients (Zhang et al 2021).…”

Section: Intratumoral Synthesis and Metabolism Of Androgensmentioning

confidence: 99%

Diverse role of androgen action in human breast cancer

et al. 2022

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Breast cancer is a hormone-dependent cancer and sex steroids play a pivotal role in breast cancer progression. Estrogens are strongly associated with breast cancers, and the estrogen receptor (estrogen receptor α; ERα) is expressed in 70–80% of human breast carcinoma tissues. Although antiestrogen therapies (endocrine therapies) have significantly improved clinical outcomes in ERα-positive breast cancer patients, some patients experience recurrence after treatment. In addition, patients with breast carcinoma lacking ERα expression do not benefit from endocrine therapy. The androgen receptor (AR) is also expressed in >70% of breast carcinoma tissues. Growing evidence supports this novel therapeutic target for the treatment of triple negative breast cancers (TNBCs) that lack ERα, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and ERα-positive breast cancers, which are resistant to conventional endocrine therapy. However, the clinical significance of AR expression is still controversial and the biological function of androgens in breast cancers is unclear. In this review, we focus on the recent findings concerning androgen action in breast cancers and the contributions of androgens to improved breast cancer therapy.

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The role of AKR1 family in tamoxifen resistant invasive lobular breast cancer based on data mining

Cited by 7 publications

References 43 publications

Identification of potential target genes of honokiol in overcoming breast cancer resistance to tamoxifen

Identification of potential target genes of honokiol in overcoming breast cancer resistance to tamoxifen

Comprehensive clinical analysis of AKR1 expression profiles in the diagnosis of human colorectal cancer

Diverse role of androgen action in human breast cancer

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