Biology subjects

Matamoros, A.

Publications and source records attributed to Matamoros, A..

2 recordsLinked to original sources

bioRxiv2025

Increased MALAT1 Levels in Thyroid Cancer are Linked to Metabolic Reprogramming and Lymphatic Infiltration in Chilean population

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) implicated in cancer progression. In thyroid cancer, MALAT1 has been proposed as a potential biomarker, but its role in disease progression remains incompletely understood. Here, we analyzed MALAT1 RNA levels in paired tumoral and adjacent non-tumoral thyroid samples from a Chilean patient cohort. We found a positive correlation of MALAT1 levels with lymphatic infiltration that was not replicated when modeling MALAT1 expression in a larger cohort obtained from the TCGA-THCA database. An exploratory RNA-seq comparison of one matched tumor-adjacent tissue pair confirmed higher tumor abundance of MALAT1 and the epithelial-to-mesenchymal transition-marker VIM, together with lower abundance of cell-adhesion gene PCDH10. To investigate the impact of MALAT1 on thyroid cancer and cellular metabolism, we targeted MALAT1 in the papillary thyroid cancer cell line TPC1. MALAT1 knock-down reduced proliferation and migration while enhancing mitochondrial respiration with no changes in glycolysis. Notably, although MALAT1 was not localized within mitochondria, its silencing modulated the expression of transcripts associated with mitochondrial dynamics and mitophagy. Consistent with these results, transcriptomic correlation analysis in the TCGA-THCA cohort showed that MALAT1 expression was largely uncoupled from oxidative phosphorylation and glycolysis gene programs, while negatively correlating with core regulators of mitophagy and mitochondrial dynamics, pointing to a link with mitochondrial quality control rather than direct bioenergetic reprogramming. Our findings highlight MALAT1 as a contributor to thyroid cancer aggressiveness and reveal a link between MALAT1 and mitochondrial quality control independent of direct mitochondrial localization. Besides, our results support a tissue-specific mechanism and population-specific role of MALAT1 in cancer biology.

cancer biology↗

bioRxiv2024

FAM162A is Crucial for Mitochondrial Structure, Dynamics, and Bioenergetics, Driving Cellular Protection and Longevity

IntroductionFAM162A is a mitochondrial protein evolutionarily conserved across taxa and ubiquitously expressed in various tissues. It is known for its role in hypoxia-induced apoptosis. However, paradoxically, FAM162A is overexpressed in cancer, where its pro-apoptotic function seems overridden, suggesting an alternative role associated with mitochondrial function and cell survival. Additionally, its precise localization and topology remain controversial. ObjectivesTo assess the role of FAM162A in mitochondrial structure, dynamics, and bioenergetics and its impact on cell viability, while establishing its precise localization, orientation, and topology. Additionally, to generate a transgenic Drosophila model overexpressing human FAM162A to evaluate its effects on organismal survival under normal and stress conditions. MethodsLocalization, orientation, and topology were determined by protease protection assays in COS7 cells. Loss-and gain-of-function experiments were performed to assess mitochondrial function and turnover by confocal microscopy, immunoblots and Seahorse technology. A transgenic Drosophila model overexpressing human FAM162A was generated to evaluate organismal survival under normal and stress conditions. ResultsFAM162A is essential for maintaining mitochondrial ultrastructure and bioenergetics, thereby influencing cell viability and stress resistance. Localization studies revealed that FAM162A resides predominantly in the inner mitochondrial membrane, particularly within the cristae, where it modulates the fusion protein OPA1. Transgenic Drosophila overexpressing human FAM162A exhibited increased lifespan and locomotor activity under both normal and heat stress conditions. ConclusionFAM162A emerges as a crucial player in maintaining mitochondrial integrity and bioenergetics. Its functional role, potentially mediated through interaction with OPA1, impacts mitochondrial health, stress resistance, cellular viability, and organismal longevity.

cell biology↗