AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway

Abstract

BackgroudAberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) has been observed during the progression of some human carcinomas. However, the expression pattern and clinical relevance of AKR1B10 in breast cancer (BC) need clarification.MethodsThe relationship between the high expression of AKR1B10 and the overall prognosis and disease-free survival of breast cancer patients was analyzed by Kaplan-Meier Plotter database. Breast cancer cell lines MCF-7/AKR1B10 stably overexpressing AKR1B10 and breast cancer cell lines BT-20/shAKR1B10 that knock down AKR1B10 were constructed, respectively. RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of AKR1B10 in breast cancer and its normal tissues. CCK8 cell proliferation assay and cell scratch test were used to detect the proliferation and migration of breast cancer cells. Western blot was used to detect the expression of proliferation-related proteins cyclinD1, c-myc, survivin and EMT-related proteins twist, snail, slug, ZEB1, E-cadherin, PI3K, p-PI3K, AKT, p-AKT, IKBα, p-IKBα, NF-κB p65, and p-NF-κB p65 proteins in breast cancer cells. The PI3K inhibitor LY94002 was used to treat MCF-7 cells to detect PI3K/AKT/NF-κB signal cascade protein Expression, and expression of NF-κB p65 in nucleoproteins and plasma proteins.ResultsIn this study, we found that AKR1B10 expression was higher in BC tissue compared to paired non-cancerous tissue. The expression of AKR1B10 positively correlated with lymph node metastasis, tumor size, Ki67 expression, and p53 expression, but inversely correlated with overall and disease-free survival rates. Gene Ontology (GO) analysis showed that AKR1B10 was closely related to cell proliferation. Overexpression of AKR1B10 facilitated proliferation and migration of BC cells in vitro in association with induction of epithelial-mesenchymal transition. Conversely, knockdown of AKR1B10 inhibited these effects. Mechanistically, silencing AKR1B10 reduced the phosphorylation of PI3K, AKT, and NF-κB p65, whereas AKR1B10 overexpression activated these signaling molecules. Indeed, PI3K inhibition attenuated NF-κB p65 nuclear localization.ConclusionsOur results demonstrate that AKR1B10 promotes proliferation and migration of BC cells and represents a novel prognostic indicator as well as a potential therapeutic target in BC.

Single-cell RNA profiling of Plasmodium vivax-infected hepatocytes reveals parasite- and host- specific transcriptomic signatures and therapeutic targets

“…S6A-D ). AKR1B10 has been implicated in cell survival through its regulation of lipid metabolism and elimination of carbonyls (Martin and Maser, 2009; Qu et al, 2021; Wang et al, 2009) and has primarily been described as a biomarker of cancer (Díez-Dacal et al, 2011; Fukumoto et al, 2005; Jin et al, 2006). More recently, it has been shown that its expression is positively correlated with non-alcoholic fatty liver disease (Govaere et al, 2020).…”

Knockdown of lncRNA FOXD2-AS1 Inhibits Proliferation, Migration, and Drug Resistance of Breast Cancer Cells

“…In addition, AKT is also associated with inflammation, immune regulation, and autophagy [ 32 ]. Studies have reported that AKR1B10 promotes breast cancer cell proliferation and migration through the PI3K/AKT/NF- κ B signaling pathway [ 33 ]. At the same time, it was found that during the development of tamoxifen resistance, the changes of PI3K/AKT molecules before matrix metallopeptidase overexpression are related to the poor prognosis of breast cancer patients [ 34 ].…”

Insights Into Transcriptome Profiles Associated With Wooden Breast Myopathy in Broilers Slaughtered at the Age of 6 or 7 Weeks

“…Increased expressions of those enzymes could be a consequence of the muscle fibers encountering stressful conditions associated with WB myopathy. In addition, an overexpression of ARK1B10 was shown to elevate β-catenin, an activator of canonical Wnt signaling, in breast cancer cell lines (Qu et al, 2019). Within this context, the findings of the present study further support the hypothesis formulated by Phillips et al (2020) in which, in the presence of WB myopathy, satellite cells could lose their capability of proliferation and differentiation due in part to an excessive activation of Wnt signaling pathway that, ultimately, results in the disruption of the muscle repair process.…”