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1. The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients

Author

Andrea Sabina Llera, Eliana Saul Furquim Werneck Abdelhay, Nora Artagaveytia, Adrián Daneri-Navarro, Bettina Müller, Carlos Velazquez, Elsa B. Alcoba, Isabel Alonso, Daniela B. Alves da Quinta, Renata Binato, Alicia Inés Bravo, Natalia Camejo, Dirce Maria Carraro, Mónica Castro, Juan M. Castro-Cervantes, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Alicia Colombo, Susanne Crocamo, Alicia Del Toro-Arreola, Raúl Delgadillo-Cisterna, Lucía Delgado, Marisa Dreyer-Breitenbach, Laura Fejerman, Elmer A. Fernández, Jorge Fernández, Wanda Fernández, Ramón A. Franco-Topete, Carolina Gabay, Fancy Gaete, Adriana Garibay-Escobar, Jorge Gómez, Gonzalo Greif, Thomas G. Gross, Marisol Guerrero, Marianne K. Henderson, Miguel E. Lopez-Muñoz, Alejandra Lopez-Vazquez, Silvina Maldonado, Andrés J. Morán-Mendoza, Maria Aparecida Nagai, Antonio Oceguera-Villanueva, Miguel A. Ortiz-Martínez, Jael Quintero, Antonio Quintero-Ramos, Rui M. Reis, Javier Retamales, Ernesto Rivera-Claisse, Darío Rocha, Robinson Rodríguez, Cristina Rosales, Efrain Salas-González, Verónica Sanchotena, Laura Segovia, Juan Martín Sendoya, Aida A. Silva-García, Alejandra Trinchero, Olivia Valenzuela, Vidya Vedham, Livia Zagame, United States-Latin American Cancer Research Network (US-LACRN), Osvaldo L. Podhajcer, Juan Abarca, Pamela Acevedo, Graciela Acosta, Gissel Acosta, Gabriela Acosta Haab, Ana Lilian Acosta Silva, Marta Aghazarian, Carola Aguayo, Bernardo Aizen, Gustavo Alarcon Lopez, Liz Almeida, Ana Alvarez, Viviane Andrade, Wenceslao Angeles-Bueno, Roberto Arai, Priscila Elvira Arambula Barreras, Ma. Isabel Aramburo Rubio, Gonzalo Ardao, Lilia A. Arellano-Jimenez, Claudia Arias, Ricardo Armisen, Mauricio Aspee, Rodrigo Assar, Itzel Reneé Astiazarán Rascón, Sebastian Astorga, Maxwell Aviles Rodriguez, Antônio Bailão Junior, Adolfo E. Barragan-Curiel, Adelfo Barragan-Ruiz, Fernanda Bermudez, Julia Bernachin, Wilfrido Bernal Herrera, Mara Bonet, Sarah Brnich, Claudio Bustamante, Miguel Angel Bustamante, Julio Bustos-Gomez, Felipe de J Bustos-Rodriguez, Janett Caballero Jasso, Angie Calfuman, Antonio Hugo José Froes Marques, Mónica Campos, Soledad Cano, Juan C. Canton-Romero, Ricardo Cappetta, Paulina Carmona, Fernando Carrizo, André Lopes Carvalho, Erika Carvallo, Julio Carzoglio, Monica Casalnuovo, Benedicta Caserta, Alvaro Castillo, César Castillo, Roger Chammas, Mario Alberto Chavez Zamudio, Loreto Chia, Elisa Chiarello, Daniela Chirico, Esther Cisneros-Quirarter, Minor Raul Cordero Bautista, Valeria Cornejo, Baldemar Corral Villegas, Andrés Cortés, Sandra Cortés, Laura Cortes-Sanabria, German Salvador Cortez Zamorano, Alejandro Corvalan, Adolfo Cruz, Alba d'Aurora, Sandra De la Fuente, Soledad De la Peña, Roberto de Leon Caballero, Mirian de Souza, César Del Castillo, Azucena Del-Toro-Valero, Mirtha Di Pretoro, Andrea Digonzelli, Jose El Ters, Paula Escobar, Marcela Estolaza, Adriane Feijo Evangelista, Marcelo Fanelli, Paulo Farias, Graciela Fernandez, José R. Filassi, Natalia Filgueiras, Diego Flaks, Edgar G. Flores-Ayala, Maria R. Flores-Marquez, David Franco Hughes, Karina Franco-Topete, Jimena Freire, Cristobal Fresno, Romina Gabrielli, Mario Gallegos, Jorge Gamboa, Daiana Ganiewich, Carlos Garbovesky, Ruben Alejandro Garcia Munguia, Ricardo Garcia-Gaeta, Alma C. Garcia-Martinez, Liliana Gimenez, Hector Gómez Silveira, Mariana M. Gomez-Del Toro, Marcela Gonzalez, Alicia Gonzalez, Germán González, Cesar Osbaldo Gonzalez Mondaca, Leivy P. Gonzalez-Ramirez, Beatriz Gonzalez-Ulloa, Susana Gorostidy, Mariela Grass, Alfonso G. Guevara Torres, Lorena Gutierrez, Susan A. Gutierrez-Rubio, Adrián Hannois, Andrew Hart, Steffen Härtel, Marcos Henriquez, Rafael Hernandez Guevara, Miriam E. Hernandez-Franco, Manuel I. Herrera-Miramontes, Graciela Horton, Gladys Ibañez, Martín Ipiña, Beatriz Jalfin, Lilian Jara, Raul Jara, Maria Luisa Jaramillo, David Javalera-Castro, Maria Eugenia Jimenez, Hugo Ju, Nazareth Juárez Rusjan, Karen Juneman, Ligia Maria Kerr, Alejandra Krupelis, Flor Esmeralda Larios-Jimenez, Jose Domingo Latorre, Guillermo Laviña, Fernando Lavista, Irma Leticia León Duarte, Alberto Lescano, Verónica Lezano, Rossana Mendoza Lopez, Jose Guillermo Lopez Cervantes, Miguel Enrique Lopez Muñoz, Dora Loria, Alejandra Luque, Alejandro Maass, Maria do Socorro Maciel, Flavia Rotea Mangone, Jorge Mansilla, Katherine Marcelain, Carolina Mariani, Marcia Maria Chiquitelli Marques, Reyna J. Martinez-Arriaga, Hector R. Martinez-Ramirez, Marcela Martins, Alma G. Maya-Gonzalez, Brenda Mazzaferri, Yadira Medina-Mora, Mariana Menini, Silvia Míguez, Soledad Milans, Soledad Montes, Ana Verónica Morales Hernández, Giberto Morga-Villela, Carla Morong, Homero Muñoz, Ignacio Miguel Muse, Carina Mussetti, Eduardo Mussetti, Luis J. Najar-Acosta, Elisa Napolitano e Ferreira, Nancy E. Navarro-Ruiz, Cristina Noblía, João Soares Nunes, Daniela Núñez, Fabiola Núñez, Nilton Onari, Emma M. Oropeza-De Anda, David Ortega Tirado, Cynthia Aparecida Bueno de Toledo Osório, Carlos Eduardo Paiva, Paulina Peñaloza, Miguel Peredo-Navarro, David Pereira, Laura Perez Michel, Francisca Pino, Tania Pino, Natalia Pinto, Jessica Pizarro, Carlos Pressa, Enrique Ramirez, Gladys E. Ramirez-Rosales, Claudia Ramis, Maritza Ramos-Ramirez, Adela Rascon Alcantar, Silvana Ravaglio, Francois Richard, Omar Rios Méndez, Ramón Enrique Robles Zepeda, Iara Santana Rocha, Natalia Rodriguez, Vilma Rodriguez, Maria Teresa Rodriguez, Diego Rodriguez-Gonzalez, Rosemeire A Roela, Ana M Romero-Gomez, Ana M Rosales-Sandoval, Omar V Rubio-Plascencia, Florencia Russo, Gaciela Sabini, Isabel Saffie, Helena Salina Dias, Brenda Guadalupe Samaniego Soto, Julio San Martino, Benito Sanchez-Llamas, Daniel Sat-Muñoz, Mariana Savignano, Cristovam Scapulatempo Neto, Max Mano Senna, Carolina Silva, Jaime Silvera, Isabele Small, Fernando Soares, Iberê Soares, Silvana Soares dos Santos, Evandro Sobrosa de Mello, José Antonio Sola, Irene Sorín, Alejandra Sosa, Anabella Sosa, Claudio Sosa, Sandra Soto, Cristiano de Pádua Souza, Lucía Spangenberg, Gustavo Steffanof, Florencia Straminsky, Mónica Tapia, Raziel O. Tapia-Llanos, Geronimo M. Tavares-Macias, Guillermo Temperley, Veronica Terzieff, Vicente Teti, Javier Tognarelli, Verónica Toledo, Paulina Toro, Roberto Torres, Mariana Torres-Palomares, Rogelio Troyo-San Roman, Hernan Urbano, Nicolas Vacca, Daniel Vaimberg, María Lourdes Valencia Peña, Maria Lujan Vaselevich, Jaime Vazquez-Nares, Ezequiel Velez-Gomez, Laura N. Venegas-Godinez, Patricia Vercelli, Ricardo Verdugo, René Aloisio da Costa Vieira, Marta Vilensky, María José Villarubias, Manuel Isaac Villegas Gómez, Stella Viña, Silvia Vornetti, Anapaula Hidemi Uema Watanabe, Carlos Zamorano, Luis Zapata, and Zdenka Zlatar

Subjects
breast cancer, Latin America, PAM50 subtypes, risk of recurrence, biological pathways, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

PurposesMost molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.Patients and MethodsWe collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes.ResultsPAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors.ConclusionsThis is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America.Clinical Trial RegistrationClinicalTrials.gov (Identifier: NCT02326857).

Published
2022
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2. Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women

Author

Liz Maria de Almeida, Sandra Cortés, Marta Vilensky, Olivia Valenzuela, Laura Cortes-Sanabria, Mirian de Souza, Rafael Alonso Barbeito, Eliana Abdelhay, Nora Artagaveytia, Adrian Daneri-Navarro, Andrea S. Llera, Bettina Müller, Osvaldo L. Podhajcer, Carlos Velazquez, Elsa Alcoba, Isabel Alonso, Alicia I. Bravo, Natalia Camejo, Dirce Maria Carraro, Mónica Castro, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Alicia Colombo, Susanne Crocamo, Alicia Del Toro-Arreola, Raul Delgadillo-Cristerna, Lucia Delgado, Marisa Dreyer Breitenbach, Elmer Fernández, Jorge Fernández, Wanda Fernández, Ramon A. Franco-Topete, Fancy Gaete, Jorge Gómez, Leivy P. Gonzalez-Ramirez, Marisol Guerrero, Susan A. Gutierrez-Rubio, Beatriz Jalfin, Alejandra Lopez-Vazquez, Dora Loria, Silvia Míguez, Andres de J. Moran-Mendoza, Gilberto Morgan-Villela, Carina Mussetti, Maria Aparecida Nagai, Antonio Oceguera-Villanueva, Rui M. Reis, Javier Retamales, Robinson Rodriguez, Cristina Rosales, Efrain Salas-Gonzalez, Laura Segovia, Juan M. Sendoya, Aida A. Silva-Garcia, Stella Viña, Livia Zagame, Beth Jones, Moysés Szklo, United States-Latin American Cancer Research Network (US-LACRN), Juan Abarca, Pamela Acevedo, Graciela Acosta, Ana Acosta, Gabriela Acosta Haab, Keyla Teresa Acosta-Torres, Marta Aghazarian, Carola Aguayo, Gustavo Alarcon-Lopez, Viviane Andrade, Wenceslao Angeles Bueno, Roberto Arai, Priscila Elvira Arambula-Barreras, Maria Isabel Arámburo-Rubio, Estrellita Araus, Gonzalo Ardao, Lilia A. Arellano-Jimenez, Felipe Argandoña, Claudia Arias, Ricardo Armisen, Mauricio Aspee, Rodrigo Assar, Itzel Reneé Astiazarán-Rascón, Sebastian Astorga, Maxwell Avilés-Rodrıguez, Antônio Bailão Junior, Adolfo E. Barragan-Curiel, Adelfo Barragan-Ruiz, Julia Bernachin, Wilfrido Bernal-Herrera, Renata Binato, Sarah Brnich, Claudio Bustamante, Miguel Angel Bustamante, Julio Bustos Gomez, Felipe de J. Bustos Rodriguez, Janett Caballero-Jasso, Angie Calfuman, Antonio Hugo, José Froes Marques Campos, Mónica Campos, Soledad Cano, Juan C. Canton-Romero, Paulina Carmona, Fernando Carrizo, Andre Lopes Carvalho, Erika Carvallo, Julio Carzoglio, Monica Casalnuovo, Benedicta Caserta, Alvaro Castillo, César Castillo, Juan M. Castro-Cervantes, Yascara Cerda, Roger Chammas, Mario Alberto Chavez-Zamudio, Loreto Chia, Daniela Chirico, Esther Cisneros-Quirarter, Minor Raul Cordero-Bautista, Valeria Cornejo, Baldemar Corral-Villegas, Andrés Cortés, German Salvador Cortez-Zamorano, Alejandro Corvalan, Adolfo Cruz, Alba d’Aurora, Sandra De la Fuente, Soledad De la Peña, Roberto de Leon-Caballero, César Del Castillo, Azucena Del-Toro-Valero, Mirtha Di Pretoro, Andrea Digonzelli, Jose El Ters, Paula Escobar, Marcela Estolaza, Adriane Feijo Evangelista, Marcelo Fanelli, Paulo Farias, Diego Flaks, Edgar G. Flores-Ayala, Maria R. Flores-Marquez, David Franco-Hughes, Karina Franco-Topete, Cristobal Fresno, Carolina Gabay, Mario Gallegos, Jorge Gamboa, Daiana Ganiewich, Carlos Garbovesky, Ricardo Garcia-Gaeta, Alma C. Garcia-Martinez, Rubén Alejandro Garcıa-Munguıa, Adriana Garibay-Escobar, Liliana Gimenez, Mariana M. Gomez-Del Toro, Germán González, César Osbaldo González Mondaca, Beatriz Gonzalez-Ulloa, Susana Gorostidy, Gonzalo Greif, Alfonso G. Guevara-Torres, Lorena Gutierrez, Adrián Hannois, Andrew Hart, Steffen Härtel, Marcos Henriquez, Miriam E Hernandez-Franco, Rafael Hernandez-Guevara, Manuel I Herrera-Miramontes, Graciela Horton, Gladys Ibañez, Martın Ipiña, Lilian Jara, Raul Jara, Maria Luisa Jaramillo, Beatriz Jardim, Maria Eugenia Jimenez, Victor M. Jimenez-Moreno, Hugo Ju, Nazareth Juárez Rusjan, Karen Juneman, Ligia Maria Kerr, Alejandra Krupelis, Guillermo Laviña, Fernando Lavista, Irma Leticia León-Duarte, Alberto Lescano, Verónica Lezano, Rossana Mendoza Lopez, Jose Guillermo López-Cervantes, Miguel Enrique Lopez-Muñoz, Francisca Lucena, Alejandra Luque, Alejandro Maass, Maria do Socorro Maciel, Silvina Maldonado, Flavia Rotea Mangone, Jorge Mansilla, Katherine Marcelain, Carolina Mariani, Marcia Maria Chiquitelli Marques, Reyna J Martinez-Arriaga, Hector R Martinez-Ramirez, Marcela Martins, Alma G Maya-Gonzalez, Mariana Menini, Soledad Milans, Soledad Montes, Ana Verónica Morales Hernández, Carla Morong, Eduardo Mussetti, Luis J Najar-Acosta, Elisa Napolitano e Ferreira, Nancy E Navarro Ruiz, Cristina Noblıa, João Soares Nunes, Fabiola Núñez, Nilton Onari, Emma M Oropeza-De Anda, David Ortega-Tirado, Miguel Angel Ortiz-Martinez, Cynthia Aparecida Bueno de Toledo Osório, Carlos Eduardo Paiva, Paulina Peñaloza, Miguel Peredo Navarro, David Pereira, Laura Perez-Michel, Francisca Pino, Tania Pino, Natalia Pinto, Jessica Pizarro, Jael Quintero, Antonio Quintero-Ramos, Enrique Ramirez, Gladys E Ramirez-Rosales, Claudia Ramis, Maritza Ramos Ramirez, Adela Rascon-Alcantar, Francois Richard, Omar Rios-Méndez, Ernesto Rivera-Claisse, Ramón E. Robles-Zepeda, Iara Santana Rocha, Natalia Rodriguez, Vilma Rodriguez, Maria Teresa Rodriguez, Diego Rodriguez-Gonzalez, Rosemeire A Roela, Ana M. Romero-Gomez, Ana M. Rosales-Sandoval, Lidia A. Rubio-Chavez, Omar V. Rubio-Plascencia, Florencia Russo, Gaciela Sabini, Isabel Saffie, Brenda Samaniego, Benito Sanchez-Llamas, Verónica Sanchotena, Daniel Sat-Muñoz, Mariana Savignano, Cristovam Scapulatempo Neto, Max Mano Senna, Carolina Silva, Jaime Silvera, Isabele Small, Fernando Soares, Iberê Soares, Silvana Soares dos Santos, Evandro Sobrosa de Mello, José Antonio Sola, Irene Sorın, Alejandra Sosa, Claudio Sosa, Cristiano de Pádua Souza, Lucıa Spangenberg, Gustavo Steffanof, Florencia Straminsky, Mónica Tapia, Raziel O. Tapia-Llanos, Geronimo M. Tavares-Macias, Veronica Terzieff, Vicente Teti, Javier Tognarelli, Verónica Toledo, Paulina Toro, Roberto Torres, Mariana Torres-Palomares, Alejandra Trinchero, Rogelio Troyo-San Roman, Hernan Urbano, Nicolas Vacca, Marıa Lourdes Valencia-Peña, Jaime Vazquez Nares, Ezequiel Velez-Gomez, Laura N. Venegas-Godinez, Ricardo Verdugo, René Aloisio da Costa Vieira, Manuel Isaac Villegas-Gómez, Silvia Vornetti, Anapaula H. U. Watanabe, Carlos Zamorano, Luis Zapata, and Zdenka Zlatar

Subjects
global excellence, oncology, Latin America, breast cancer, molecular subtypes, risk factors, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher’s exact tests and the OS by Kaplan–Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

Published
2022
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3. Competing endogenous RNAs in human astrocytes: crosstalk and interacting networks in response to lipotoxicity

Author

Natalia Gil-Jaramillo, Andrés Felipe Aristizábal-Pachón, María Alejandra Luque Aleman, Valentina González Gómez, Hans Deyvy Escobar Hurtado, Laura Camila Girón Pinto, Juan Sebastian Jaime Camacho, Alexis Felipe Rojas-Cruz, Yeimy González-Giraldo, Andrés Pinzón, and Janneth González

Subjects
ceRNA (lncRNA–miRNA–mRNA), Transcriptome (RNA-seq), lipotoxicity, neurodegeneration, astrocyte, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Neurodegenerative diseases (NDs) are characterized by a progressive deterioration of neuronal function, leading to motor and cognitive damage in patients. Astrocytes are essential for maintaining brain homeostasis, and their functional impairment is increasingly recognized as central to the etiology of various NDs. Such impairment can be induced by toxic insults with palmitic acid (PA), a common fatty acid, that disrupts autophagy, increases reactive oxygen species, and triggers inflammation. Although the effects of PA on astrocytes have been addressed, most aspects of the dynamics of this fatty acid remain unknown. Additionally, there is still no model that satisfactorily explains how astroglia goes from being neuroprotective to neurotoxic. Current incomplete knowledge needs to be improved by the growing field of non-coding RNAs (ncRNAs), which is proven to be related to NDs, where the complexity of the interactions among these molecules and how they control other RNA expressions need to be addressed. In the present study, we present an extensive competing endogenous RNA (ceRNA) network using transcriptomic data from normal human astrocyte (NHA) cells exposed to PA lipotoxic conditions and experimentally validated data on ncRNA interaction. The obtained network contains 7 lncRNA transcripts, 38 miRNAs, and 239 mRNAs that showed enrichment in ND-related processes, such as fatty acid metabolism and biosynthesis, FoxO and TGF-β signaling pathways, prion diseases, apoptosis, and immune-related pathways. In addition, the transcriptomic profile was used to propose 22 potential key controllers lncRNA/miRNA/mRNA axes in ND mechanisms. The relevance of five of these axes was corroborated by the miRNA expression data obtained in other studies. MEG3 (ENST00000398461)/hsa-let-7d-5p/ATF6B axis showed importance in Parkinson’s and late Alzheimer’s diseases, while AC092687.3/hsa-let-7e-5p/[SREBF2, FNIP1, PMAIP1] and SDCBP2-AS1 (ENST00000446423)/hsa-miR-101-3p/MAPK6 axes are probably related to Alzheimer’s disease development and pathology. The presented network and axes will help to understand the PA-induced mechanisms in astrocytes, leading to protection or injury in the CNS under lipotoxic conditions as part of the intricated cellular regulation influencing the pathology of different NDs. Furthermore, the five corroborated axes could be considered study targets for new pharmacologic treatments or as possible diagnostic molecules, contributing to improving the quality of life of millions worldwide.

Published
2023
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