RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model

Author(s)

Jardim-Perassi, Bruna Victorasso ^[1] ; Alexandre, Pamela A. ^[2] ; Sonehara, Nathalia M. ^[1] ; de Paula-Junior, Rubens ^[1] ; Reis Junior, Osvaldo ^[3] ; Fukumasu, Heidge ^[2] ; Chammas, Roger ^[4] ; Coutinho, Luiz Lehmann ^[5] ; Pires de Campos Zuccari, Debora Aparecida ^[1]

Affiliation

^[1] Fac Med Sao Jose do Rio Preto, Ave Brigadeiro Faria Lima 5419, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Zootecnia & Engn Alimentos, Ave Duque Caxias Norte 225, BR-13635900 Pirassununga, SP - Brazil

^[3] Univ Estadual Campinas, Inst Biol, Cidade Univ Zeferino Vaz Barao Geraldo, BR-13083970 Campinas, SP - Brazil

^[4] Univ Sao Paulo, Fac Med, Ave Dr Arnaldo 251, 8th Floor, BR-01246000 Sao Paulo, SP - Brazil

^[5] Escola Super Agr Luis Dequeiroz, Ave Padua Dias 11, BR-13418900 Piracicaba, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 9, JAN 30 2019.
• Web of Science Citations: 3

Abstract

Melatonin is a pleiotropic anti-cancer molecule that controls cancer growth by multiple mechanisms. RNA-Seq can potentially evaluate therapeutic response and its use in xenograft tumor models can differentiate the changes that occur specifically in tumor cells or in the tumor microenvironment (TME). Melatonin actions were evaluated in a xenograft model of triple-negative breast cancer. Balb/c nude mice bearing MDA-MB-231 tumors were treated with melatonin or vehicle. RNA-Seq was performed on the Illumina HiSeq. 2500 and data were mapped against human and mouse genomes separately to differentiate species-specific expression. Differentially expressed (DE) genes were identified and Weighted Gene Co-expression Network Analysis (WGCNA) was used to detect clusters of highly coexpressed genes. Melatonin treatment reduced tumor growth (p < 0.01). 57 DE genes were identified in murine cells, which represented the TME, and were mainly involved in immune response. The WGCNA detected co-expressed genes in tumor cells and TME, which were related to the immune system among other biological processes. The upregulation of two genes (Tnfaip8l2 and Il1f6) by melatonin was validated in the TME, these genes play important roles in the immune system. Taken together, the transcriptomic data suggests that melatonin anti-tumor actions occur through modulation of TME in this xenograft tumor model. (AU)

• FAPESP's process: 14/13815-5 - Radiomics and transcriptomics analysis of breast cancer in an animal model after melatonin treatment
• Grantee: Bruna Victorasso Jardim-Perassi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral