The effects of fumonisin B1 on intercellular communications and miRNA modulations: Non-genotoxic carcinogenesis mechanisms in human kidney cells

Karaman E. F., Abudayyak M. F., Guler Z. R., Bektas S., Kaptan E., Ozden S.

Toxicology, cilt.509, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 509
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.tox.2024.153968
  • Dergi Adı: Toxicology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Communication Abstracts, Environment Index, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Anahtar Kelimeler: Epigenetics, Fumonisin B1, Gap junctions, MiRNA
  • İstanbul Üniversitesi Adresli: Evet

Özet

Fumonisin B1 (FB1), which is produced by Fusarium species, is one of the most prevalent mycotoxins known to exert several toxic effects, particularly nephrotoxicity. While its genotoxic carcinogenic mechanisms have been extensively studied, its influence on non-genotoxic pathways including intercellular communication and microRNA (miRNA) regulation remain underexplored. The present study investigates the effects of FB1 on gap junctions, miRNA expression profiles, and their relationship in human kidney cells (HK-2 and HEK293). Both cell lines showed increased apoptosis rates at 50 and 100 µM, while FB1 exposure significantly reduced gap junctional intercellular communication (GJIC) and decreased the expression levels of related genes, including Cx43, Cx45, e-cadherin, Cadherin-2, and β-catenin. After FB1 treatments alteration on the regulation of miRNAs including let-7a-5p, miR-125a-5p, miR-222–3p, miR-92a-3p, let-7b-5p, let-7e-5p, miR-21–5p, miR-155–5p, let-7i-5p, let-7d-5p, let-7f-5p, miR-181b-5p, miR-15b-5p, miR-23b-3p, miR-20b-5p, miR-196a-5p miRNAs have been shown. Let-7a-5p was selected among the altered miRNAs to elucidate the relationship between miRNAs and GJIC after FB1 exposure as it is one of the common miRNAs that changes in both cell lines and one of its target genes is Cx45, which is an important gene for GJIC. However, transfection analysis did not show any differences, resulting in Cx45 not being a direct target of let-7a-5p in HK-2 and HEK-293 cells. Through comprehensive analysis, we elucidated that FB1's impact on intercellular signaling cascades and its regulatory role on miRNA expression profiles, offering valuable insights into carcinogenesis beyond traditional genotoxic paradigms. Understanding these mechanisms is crucial for elucidating the mechanisms of FB1-induced toxicity.