Assessing the link between diabetic metabolic dysregulation and breast cancer progression

AHMED, Samrein B. M., RADWAN, Nada, AMER, Sara, SAHEB SHARIF-ASKARI, Narjes, MAHDAMI, Amena, SAMARA, Kamel A., HALWANI, Rabih and JELINEK, Herbert F. (2023). Assessing the link between diabetic metabolic dysregulation and breast cancer progression. International Journal of Molecular Sciences, 24 (14): 11816.

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Abstract

Diabetes mellitus is a burdensome disease that affects various cellular functions through altered glucose metabolism. Several reports have linked diabetes to cancer development; however, the exact molecular mechanism of how diabetes-related traits contribute to cancer progression is not fully understood. The current study aimed to explore the molecular mechanism underlying the potential effect of hyperglycemia combined with hyperinsulinemia on the progression of breast cancer cells. To this end, gene dysregulation induced by the exposure of MCF7 breast cancer cells to hyperglycemia (HG), or a combination of hyperglycemia and hyperinsulinemia (HGI), was analyzed using a microarray gene expression assay. Hyperglycemia combined with hyperinsulinemia induced differential expression of 45 genes (greater than or equal to two-fold), which were not shared by other treatments. On the other hand, in silico analysis performed using a publicly available dataset (GEO: GSE150586) revealed differential upregulation of 15 genes in the breast tumor tissues of diabetic patients with breast cancer when compared with breast cancer patients with no diabetes. SLC26A11, ALDH1A3, MED20, PABPC4 and SCP2 were among the top upregulated genes in both microarray data and the in silico analysis. In conclusion, hyperglycemia combined with hyperinsulinemia caused a likely unique signature that contributes to acquiring more carcinogenic traits. Indeed, these findings might potentially add emphasis on how monitoring diabetes-related metabolic alteration as an adjunct to diabetes therapy is important in improving breast cancer outcomes. However, further detailed studies are required to decipher the role of the highlighted genes, in this study, in the pathogenesis of breast cancer in patients with a different glycemic index.

Item Type:	Article
Additional Information:	** Article version: VoR ** From MDPI via Jisc Publications Router ** Licence for VoR version of this article: https://creativecommons.org/licenses/by/4.0/ ** Peer reviewed: TRUE ** Acknowledgements: Acknowledgments: We acknowledge Genotypic Technology Private Limited Bangalore for the microarray processing and data analysis reported in this publication. **Journal IDs: eissn 1422-0067 **Article IDs: publisher-id: ijms-24-11816 **History: published_online 23-07-2023; accepted 20-07-2023; rev-recd 19-07-2023; submitted 05-07-2023; collection 07-2023
Uncontrolled Keywords:	diabetes, breast cancer, hyperinsulinemia, hyperglycemia, gene dysregulation
Identification Number:	https://doi.org/10.3390/ijms241411816
SWORD Depositor:	Colin Knott
Depositing User:	Colin Knott
Date Deposited:	11 Aug 2023 08:57
Last Modified:	11 Oct 2023 12:45
URI:	https://shura.shu.ac.uk/id/eprint/32244

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