Browsing by Author "Landeros, Natalia"

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    A Single Variant in Pri-miRNA-155 Associated with Susceptibility to Hereditary Breast Cancer Promotes Aggressiveness in Breast Cancer Cells
    (2022) Landeros, Natalia; Gonzalez-Hormazabal, Patricio; Perez-Moreno, Pablo; Tapia, Julio C.; Jara, Lilian
    Variants in genes encoding for microRNAs have been associated with their deregulation in breast cancer (BC). Sequencing of microRNAs deregulated in BC was performed using DNA from Chilean patients with a strong family history and negative for mutations in BRCA1/BRCA2. Seventeen variants were identified, three of which were selected for a case-control association study: rs376491654 (miR-335), rs755634302 (miR-497), and rs190708267 (miR-155). For rs190708267 C>T, the heterozygous T allele was detected in four BC cases and absent in controls, while homozygous TT cases were not detected. Variants were modelled in silico, cloned in a plasmid, expressed in BC cell lines, and functional in vitro assays were performed. Overexpression of the miR-155-T allele increased mature miR-155-5p levels in both BC cell lines, suggesting that its presence alters pre-miR-155 processing. Moreover, BC cells overexpressing the miR-155-T allele showed increased proliferation, migration, and resistance to cisplatin-induced death compared to miR-155-C overexpressing cells. Of note, the 3 ' UTR of APC, GSK3 beta, and PPP1CA genes, all into the canonical Wnt signaling pathway, were identified as direct targets. APC and GSK3 beta mRNA levels decreased while PP1 levels increased. These results suggest a pathogenic role of the variant rs190708267 (miR-155) in BRCA 1/2 negative BC, conferring susceptibility and promoting traits of aggressiveness.
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    Exposure to pesticides in Chile and its relationship with carcinogenic potential: a review
    (Frontiers Media SA, 2025) Munoz-Quezada, María Teresa; Iglesias, Verónica; Zúñiga-Venegas, Liliana; Pancetti, Floria; Foerster, Claudia; Landeros, Natalia; Lucero, Boris; Schwantes, Daniel; Cortes Arancibia, Sandra Isabel
    Background: The widespread application of pesticides in agriculture and the consequent heightened human exposure to these potentially harmful substances present considerable environmental and health risks. The potential link to cancer is particularly concerning, underscoring the urgent need for more sustainable and health-conscious agricultural practices. Pesticides are pervasive global contaminants, with exposure occurring through various routes. Improper use is associated with genotoxicity, neurobehavioral problems, thyroid dysfunction, reproductive issues, and cancer, among other deleterious damages. While pesticide exposure is evident in Chile, a direct link to cancer remains uncertain. Objective: To examine the scientific evidence on pesticides exposure in the environment and human populations, and its relationship with cancer in Chilean territory. Methods: The search for original articles was performed in international peer-reviewed scientific databases, including Scopus, Web of Science (WoS), and PubMed Advanced Search Builder. Following the PRISMA extension for review guidelines, the search included studies on environmental pesticide exposure, human biomarker assessments, experimental investigations, and the potential pesticide-cancer associations in Chile. Foreign studies, systematic reviews, and meta-analyses were excluded. Results: Among the 83 qualifying studies conducted between 1996 and 2024, elevated pesticide exposure risks were documented, with 71% indicating high concentrations that may pose health risk. Additionally, 20% of studies reported significant chlorinated compounds, including organochlorines (OCs) and polychlorinated biphenyls (PCBs), while 79.5% identified carcinogenic to humans classified by the International Agency for Research on Cancer. The review emphasizes the urgent need to update pesticide-related regulations in Chile, including implementing bans or restrictions on carcinogenic pesticides and establishing stricter standards for allowable pesticide residue levels in food. Conclusion: Long-term epidemiological studies are essential to establishing concrete links between pesticide exposure and specific types of cancer. Additionally, investigating epigenetic markers associated with pesticide exposure, especially in occupational settings, is critical. Furthermore, allocating resources and prioritizing further research is fundamental, particularly in regions with substantial agricultural exposure.
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    Novel Risk Associations between microRNA Polymorphisms and Gastric Cancer in a Chilean Population
    (2022) Landeros, Natalia; Corvalán R., Alejandro; Musleh, Maher; Quinones, Luis A.; Varela, Nelson M.; Gonzalez Hormazabal, Patricio
    Gastric cancer (GC) is the fifth leading cause of cancer deaths in the world, with variations across geographical regions and ethnicities. Emerging evidence indicates that miRNA expression is dysregulated in GC and its polymorphisms may contribute to these variations, which has yet to be explored in Latin American populations. In a case-control study of 310 GC patients and 311 healthy donors from Chile, we assessed the association of 279 polymorphisms in 242 miRNA genes. Two novel polymorphisms were found to be associated with GC: rs4822739:C>G (miR-548j) and rs701213:T>C (miR-4427). Additionally, rs1553867776:T>TCCCCA (miR-4274) and rs12416605:C>T (miR-938) were associated with intestinal-type GC, and rs4822739:C>G (miR-548j) and rs1439619:T>G (miR-3175) with TNM I-II stage. The polymorphisms rs6149511:T> TGAAGGGCTCCA (miR-6891), rs404337:G>A (miR-8084), and rs1439619:T>G (miR-3175) were identified among H.pylori-infected GC patients and rs7500280:T>C (miR-4719) and rs1439619:T>G (miR-3175) were found among H. pylori cagPAI+ infected GC cases. Prediction analysis suggests that seven polymorphisms could alter the secondary structure of the miRNA, and the other one is located in the seed region of miR-938. Targets of miRNAs are enriched in GC pathways, suggesting a possible biological effect. In this study, we identified seven novel associations and replicated one previously described in Caucasian population. These findings contribute to the understanding of miRNA genetic polymorphisms in the GC pathogenesis.