Person: Perez Moreno, Pablo
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Perez Moreno
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Pablo
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Publication Molecular Interplay Between Non-Coding RNAs and Connexins and Its Possible Role in Cancer(2025) Perez Moreno, Pablo; Muñoz, Juan; Retamal, Mauricio A.Non-coding RNAs (ncRNAs) are sequences that do not encode for proteins and play key roles in different cellular processes, including cell proliferation and differentiation. On the other hand, connexins (Cxs) are transmembrane proteins that principally allow intercellular communication. In pathological conditions such as cancer, there is a deregulation in the expression and/or function of ncRNAs and Cxs, which in turn leads to an enhancement in the aggressive phenotype, such as a greater proliferative and invasive capacity. This suggests a plausible interplay between ncRNAs and Cxs. Based on that, this review aims to summarize the current knowledge regarding this relationship and to analyze how it may influence the development of aggressive traits in cancer cells and the clinicopathological features of cancer patients. Finally, we discuss the potential of ncRNAs and Cxs as promising clinical biomarkers for cancer diagnosis, prognosis, and therapeutic targeting. Keywords: cancer; connexins; non-coding RNAs.Publication The Role of MicroRNAs in Breast Cancer and the Challenges of Their Clinical Application(2023) Muñoz, Juan P.; Perez Moreno, Pablo; Pérez, Yasmín; Calaf, Gloria M.MicroRNAs (miRNAs) constitute a subclass of non-coding RNAs that exert substantial influence on gene-expression regulation. Their tightly controlled expression plays a pivotal role in various cellular processes, while their dysregulation has been implicated in numerous pathological conditions, including cancer. Among cancers affecting women, breast cancer (BC) is the most prevalent malignant tumor. Extensive investigations have demonstrated distinct expression patterns of miRNAs in normal and malignant breast cells. Consequently, these findings have prompted research efforts towards leveraging miRNAs as diagnostic tools and the development of therapeutic strategies. The aim of this review is to describe the role of miRNAs in BC. We discuss the identification of oncogenic, tumor suppressor and metastatic miRNAs among BC cells, and their impact on tumor progression. We describe the potential of miRNAs as diagnostic and prognostic biomarkers for BC, as well as their role as promising therapeutic targets. Finally, we evaluate the current use of artificial intelligence tools for miRNA analysis and the challenges faced by these new biomedical approaches in its clinical application. The insights presented in this review underscore the promising prospects of utilizing miRNAs as innovative diagnostic, prognostic, and therapeutic tools for the management of BC.Publication Management of chronic pleural tuberculosis and non-tuberculous empyema in the 21st century(2024) Perez Moreno, Pablo; Bello, AngelicaThis review addresses complexities in managing pleural tuberculosis (TB) and non-TB empyema. Historically, TB, often termed “the mother of thoracic surgery”, has witnessed a dramatic transformation from invasive surgical interventions to the dominance of medical therapy with the advent of effective anti- TB agents in the mid-20th century. This shift marked a pivotal moment in the treatment landscape, with medical therapy taking precedence and surgical methods reserved for diagnostic purposes or complications. In contrast, the history of non-TB empyema, dating back to Aristotle, evolved from open drainage and open surgery to minimally invasive surgery and fibrinolytic therapy. The review delves into the nuances of these conditions, exploring their clinical manifestations and the state-of-the-art management strategies that have emerged over time. Advancements in imaging modalities, such as computed tomography (CT), complemented by diagnostic laboratory techniques like the GeneXpert MTB/RIF assay, have revolutionized the diagnosis of TB, enhancing accuracy and expediting the process. The review also highlights the distinct clinical presentations of pleural TB and non-TB empyema, underscoring the challenges and intricacies in their management. It thoroughly explores the historical evolution, current diagnostic approaches, and advanced management strategies for these conditions, offering valuable insights for the learner.Publication LINC00662 Promotes Aggressive Traits by Modulating OCT4 Expression through miR-335-5p in Gallbladder Cancer Cells(2024) Perez Moreno, Pablo; Riquelme, Ismael; Bizama, Carolina; Vergara, Luis; Tapia, Julio; Brebi, Priscilla; García, Patricia; Roa, JuanPublication Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator(2025) Fernández, Ainoa; Orellana, Viviana; Llanquinao, Jesús; Nuñez, Gonzalo; Perez Moreno, Pablo; Contreras, Sebastián; Martin, Alberto; Mammano, Fabio; Alfaro, Ivan; Calderón, Juan; Stehberg, Jimmy; Sáez, Mauricio; Retamal, Mauricio A.Background: Oncogenes drive cancer progression, but few are active exclusively in tumor cells. Connexins (Cxs), traditionally recognized as ion channel proteins, can localize to the nucleus and regulate gene expression, playing key roles in both physiological and pathological processes. Cx46, once thought to be restricted to the eye lens, has been implicated in tumor growth, though its underlying mechanisms remain unclear. This study investigates the nuclear presence of Cx46 in cancer cells and its potential role as a transcriptional modulator. Methods: We employed ChIP-Seq, confocal immunofluorescence, and nuclear protein purification to assess Cx46 localization and DNA interactions. Functional assays were conducted to evaluate its effects on invasion, division, spheroid formation, and mesenchymal marker expression. Single-point mutations and molecular dynamics simulations were used to explore potential Cx46-DNA interactions. Results: Cx46 mRNA upregulation was found in a variety of tumors compared to adjacent healthy tissue. In HeLa cells, which do not express Cx46, its transfection promoted proliferation, invasion and self-renewal capacity, cancer stem cell traits and mesenchymal features. Consistently, in Sk-Mel-2, which naturally express Cx46, reduced Cx46 expression led to a decrease in the similar parameters. In HeLa cells, nuclear Cx46 was detected in two forms, full length 46 kDa and a 30 kDa fragment (GJA3-30 k), ChIP-Seq experiments revealed that Cx46 binds to the DNA at intergenic and promoter regions, leading to the activation of oncogenic pathways. Molecular dynamics simulations suggest that GJA3-30 k dimerizes in a RAD50-like structure, forming stable DNA complexes. Cx46 and in some cases GJA3-30 k were detected in the nuclei of multiple cancer cell lines, including prostate, breast and skin cancers. Conclusions: Our findings reveal a novel nuclear role for Cx46 in cancer, demonstrating its function as a transcriptional regulator and its potential as a therapeutic target.