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Abstract Increasing evidence suggests that mitophagy is crucially involved in the progression of polycystic ovary syndrome (PCOS). Exploration of PCOS-specific biomarkers related to mitophagy is expected to provide critical insights into disease pathogenesis. In this study, we employed bioinformatic analyses and machine learning algorithms to determine novel biomarkers for PCOS that may be tied with mitophagy. A grand total of 12 differential expressed mitophagy-related genes (DE‐MRGs) associated with PCOS were identified. TOMM5 and MAP1LC3A among the 12 DE‐MRGs were recognized as potential marker genes by LASSO, RF and SVM‐RFE algorithms. The area under the ROC curve (AUROC) of MAP1LC3A were all greater than 0.8 both in the training set and validation sets. The CIBERSORT analysis indicated a potential association between alterations in the immune microenvironment of PCOS individuals and MAP1LC3A expression. In addition, we found that MAP1LC3A was positively related to the testosterone levels of PCOS patients. Overall, MAP1LC3A was identified as optimal PCOS-specific biomarkers related to mitophagy. Our findings created a diagnostic strength and offered a perspective for investigating the mitophagy process in PCOS.

Increasing evidence suggests that mitophagy is crucially involved in the progression of polycystic ovary syndrome (PCOS). Exploration of PCOS-specific biomarkers related to mitophagy is expected to provide critical insights into disease pathogenesis. In this study, we employed bioinformatic analyses and machine learning algorithms to determine novel biomarkers for PCOS that may be tied with mitophagy. A grand total of 12 differential expressed mitophagy-related genes (DE‐MRGs) associated with PCOS were identified. TOMM5 and MAP1LC3A among the 12 DE‐MRGs were recognized as potential marker genes by LASSO, RF and SVM‐RFE algorithms. The area under the ROC curve (AUROC) of MAP1LC3A were all greater than 0.8 both in the training set and validation sets. The CIBERSORT analysis indicated a potential association between alterations in the immune microenvironment of PCOS individuals and MAP1LC3A expression. In addition, we found that MAP1LC3A was positively related to the testosterone levels of PCOS patients. Overall, MAP1LC3A was identified as optimal PCOS-specific biomarkers related to mitophagy. Our findings created a diagnostic strength and offered a perspective for investigating the mitophagy process in PCOS. [ABSTRACT FROM AUTHOR]

Background: Autophagy is a catabolic process whereby organelles and long-lived proteins are recycled through lysosomes to maintain cellular homeostasis. This process is being widely studied using culture techniques and animal models; however, cervicovaginal smears have not been used to detect autophagy. Aims: Our study aims to detect and evaluate autophagy in normal, malignant, infectious, and atypical cells in cervicovaginal smears by using cytological and immunocytochemical methods. Materials and Methods: Papanicolaou-stained 200 cervicovaginal smears were examined and 55 of 200 (27.5%) smears containing negative for intraepithelial lesion or malignancy (NILM) with identifiable infections and/or reactive/reparative changes (INF); briefly, NILM-INF (n = 31, 56.4%), atypical (n = 4, 7.3%), and malignant cells (n = 20, 36.3%) were evaluated as a study group. One hundred forty-five of 200 (72.5%) normal smears were accepted as the NILM without any identifiable infections (control group). The autophagy marker protein Microtubule-associated protein 1 light chain 3 A (MAP1LC3A) was used for immunocytochemical examination. Results: The staining intensity of the MAP1LC3A protein and autophagy positivity were lower in the malignant cells; however, they were higher in the NILM-INF and atypical cells. A statistically significant correlation between the malignant and normal cells was obtained for the autophagy positivity (P = 0.012). In view of the staining intensity of MAP1LC3A protein by the H-score method, a significant correlation was found between the NILM-INF and the normal cells (P = 0.015). Conclusions: Autophagy was detected in various cervicovaginal smears for the first time in this study. Our findings indicate that an autophagy process is essential in infectious cells as well as in the transformation of atypical cells into malignant cells in carcinogenesis. [ABSTRACT FROM AUTHOR]

Autophagy is an effective regulatory process for eliminating tumors and worn-out intracellular components. Different groups of enzymes and regulatory elements are involved in the autophagy process. MAP1LC3A and BECN1 genes are the most important gene groups in autophagy. These genes, through the production of beclin-1 and lc3 proteins, are involved in the production of autophagosomes. In general, both MAP1LC3A and BECN1 genes are active in cellular responses and the biological process. The aim of this study was bioinformatics analysis at the level of genome and proteome and to evaluate and compare the expression of MAP1LC3A and BECN1 genes in different human body tissues. The results of this study showed that the expression level of the BECN1 gene was relatively higher than the MAP1LC3A gene in different mammals. Cell analysis of MAP1LC3A and BECN1 genes by antibodies that bind to proteins of target genes showed that the protein encoded by the BECN1 gene is more present in the cytosol and the proteins encoded by MAP1LC3A gene are locally present in vesicles. It was also found that the protein encoded by the MAP1LC3A gene had a higher expression in brain tissues than in other tissues, while the beclin-1 protein in cardiac tissue showed higher expression than in other tissues. Finally, by using this information, it is possible to provide the ground for targeted therapies.

Breast cancer is the second most common cancer after skin cancer and one of the leading causes of death among women. Thymol has antioxidant, apoptotic, anti-cancer, and anti-inflammatory properties. In this study iron oxide nanoparticles were synthetized by chemical co-precipitation method, then were coated with chitosan and thymol was loaded on them. The properties and characteristics of these compounds were investigated by FE-SEM, DLS and, zeta potential techniques. Finally, the release and encapsulation behavior of these compounds was calculated. The anti-cancer effect of thymol loaded chitosan-coated Fe3O4 nanoparticles was investigated by the MTT method. The rate of apoptosis was assessed by flow cytometry test, while BAX and BCL2 were assessed by ELISA test. The expression of the MAP1LC3A gene was also examined by the Real-time PCR technique. The results of MTT, ELISA, flow cytometry and, Real time PCR techniques showed that thymol loaded chitosan-coated Fe3O4 nanoparticles at concentration of 50 μg/mL 48-h treatment had the most effect on cytotoxicity, apoptosis, and autophagy, hence this compound probably has anti-cancer properties on the MDA-MB-231 cell line by activating the autophagy and apoptosis pathways. [ABSTRACT FROM AUTHOR]

The unfolded protein response pathways (UPR), autophagy, and compartmentalization of misfolded proteins into inclusion bodies are critical components of the protein quality control network. Among inclusion bodies, aggresomes are particularly intriguing due to their association with cellular survival, drug resistance, and aggresive cancer behavior. Aggresomes are molecular condensates formed when collapsed vimentin cages encircle misfolded proteins before final removal by autophagy. Yet significant gaps persist in the mechanisms governing aggresome formation and elimination in cancer cells. Understanding these mechanisms is crucial, especially considering the involvement of LC3A, a member of the MAP1LC3 family, which plays a unique role in autophagy regulation and has been reported to be epigenetically silenced in many cancers. Herein, we utilized the tetracycline-inducible expression of LC3A to investigate its role in choroid plexus carcinoma cells, which inherently exhibit the presence of aggresomes. Live cell imaging was employed to demonstrate the effect of LC3A expression on aggresome-positive cells, while SILAC-based proteomics identified LC3A-induced protein and pathway alterations. Our findings demonstrated that extended expression of LC3A is associated with cellular senescence. However, the obstruction of lysosomal degradation in this context has a deleterious effect on cellular viability. In response to LC3A-induced autophagy, we observed significant alterations in mitochondrial morphology, reflected by mitochondrial dysfunction and increased ROS production. Furthermore, LC3A expression elicited the activation of the PERK-eIF2α-ATF4 axis of the UPR, underscoring a significant change in the protein quality control network. In conclusion, our results elucidate that LC3A-mediated autophagy alters the protein quality control network, exposing a vulnerability in aggresome-positive cancer cells., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)