RNA-sequencing-based Gene Expression Profile Revealing Breast Tumor Development Induced by Exposure of Bisphenol S

Abstract

Aberrant biological information occurs naturally at exposure to bisphenol A or its alternatives, which was associated with the occurrence and development of breast cancer. However, the potential molecular variation in gene expression during the breast tumor development is still unclear. Herein, high throughput RNA sequencing(RNA-Seq) and bioinformatics analysis were used to investigate the variation of tumor-mRNA profile exposed with BPS5 (5 µg/kg bw/day) or BPS50(50 µg/kg bw/day) in tumor development-associated MMTV-PyMT transgenic mouse model. Meanwhile, we analyzed the dose-effects of bisphenol S(BPS) and BPS-induced tumor development on the gene level exhaustively. In dose-effect aspects of BPS, the increased concentration of BPS significantly changed the numbers and enrichment pathway of differentially expressed genes(DEGs), especially the enrichment pathways involved in up-regulated genes including ribosome, peroxisome proliferators-activated receptor(PPAR) signaling pathway and progesterone-mediated oocyte maturation pathway. In effects of BPS exposure to tumor development, expression of IgκC, Zfp385b, Cldn10, Pgr and Snord14d has changed significantly throughout the tumor development. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) results obtained from BPS-induced tumor development showed that the functional classifications were intensively altered with an extension of time in high-dose BPS groups. The acquired DEGs and pathway information could help with the accurate exploration of molecular mechanisms of tumor development, screening of molecular targets of breast cancer, and toxicological evaluation of environmental pollutants.

Keywords

Bisphenol S / RNA-sequencing / Breast cancer / Tumor development

References

[1] Brody J G, Rudel R A. Environ. Health. Perspect., 2003, 111: 1007.

[2] Zhao C, Yong T, Zhang Y B, Xiao Y, Jin Y F, Zheng C, Nirasawa T, Cai Z W. J. Hazard. Mater., 2021, 414: 125391.

[3] Rochester J R, Bolden A L. Environ. Health. Perspect., 2015, 123: 643.

[4] Zalko D, Jacques C, Duplan H, Bruel S, Perdu E. Chemosphere., 2011, 82: 424.

[5] Acevedo N, Davis B, Schaeberle C M, Sonnenschein C, Soto A M. Environ. Health. Perspect., 2013, 121: 1040.

[6] Ayyanan A, Laribi O, Schuepbach-Mallepell S, Schrick C, Gutierrez M, Tanos T, Lefebvre G, Rougemont J, Yalcin-Ozuysal O, Brisken C. Mol. Endocrinol., 2011, 25: 1915.

[7] Murray I J, Maffini M V, Ucci A A, Sonnenschein C, Soto A M. Reprod. Toxicol., 2007, 23: 383.

[8] Zhao C, Xie P S, Wang H L, Cai Z W. J. Hazard. Mater., 2018, 358: 503.

[9] Zhao C, Xie P S, Yong T, Wang H L, Chung A C K, Cai Z W. Anal. Chem., 2018, 90: 3196.

[10] Mesnage R, Phedonos A, Arno M, Balu S, Corton C, Antoniou M N. Toxicol. Sci., 2017, 158: 431.

[11] Jung J, Mok C, Lee W, Jang W. Mol. Cell. Toxicol., 2017, 13: 239.

[12] Zhao C, Tang Z, Yan J C, Fang J, Wang H L, Cai Z W. Sci. Total Environ., 2017, 592: 357.

[13] Zhao C, Xie P S, Yang T, Wang H L, Chung A C K, Cai Z W. Chin. Chem. Lett., 2018, 29: 1281.

[14] Liao J, Li J, Cheng H, Chen Y, Mo Z. Medicine, 2018, 97: e13187.

[15] Sun H, Cui C, Xiao F, Wang H, Xu J, Shi X F, Yang Y F, Zhang Q W, Zheng X F, Yang X M, Wu C, Wang L S. Hepatol. Res., 2015, 45: 1312.

[16] Barros-Filho M C, Marchi F A, Pinto C A, Rogatto S R, Kowalski L P. J. Clin. Endocrinol. Metab., 2015, 100: E890.

[17] Vang A., Salem K., Fowler A. M., Endocrinology., 2023, doi:https://doi.org/10.1210/endocr/bqad020

[18] Ghali R M, Al-Mutawa M A, Ebrahim B H, Jrah H H, Zaied S, Bhiri H, Hmila F, Mahjoub T, Almawi W Y. Pathol. Oncol. Res., 2020, 26: 141.

[19] Whiteside T L, Ferrone S. Clin. Cancer. Res., 2013, 19: 305.

[20] Pandey J P, Kistner-Griffin E, Black L, Namboodiri A M, Iwasaki M, Kasuga Y, Hamada G S, Tsugane S. Immunobiology., 2014, 219: 113.

[21] Schmidt M, Hellwig B, Hammad S, Othman A, Lohr M, Chen Z, Boehm D, Gebhard S, Petry I, Lebrecht A, Cadenas C, Marchan R, Stewart J D, Solbach C, Holmberg L, Edlund K, Kultima H G, Rody A, Berglund A, Lambe M, Isaksson A, Botling J, Karn T, Müller V, Gerhold-Ay A, Cotarelo C, Sebastian M, Kronenwett R, Bojar H, Lehr H, Sahin U, Koelbl H, Gehrmann M, Micke P, Rahnenführer J, Hengstler J G. Clin. Cancer. Res., 2012, 18: 2695.