The Phosphatase and Tensin Homolog gene (PTEN) is pivotal in regulating diverse cellular processes, including growth, differentiation, proliferation, and cell survival, mainly by modulating the PI3K/AKT/mTOR pathway. Alterations in the expression of the PTEN gene have been associated with epigenetic mechanisms, particularly the regulation by small non-coding RNAs, such as miRNAs. Modifications in the expression levels of miRNAs that control PTEN have been shown to lead to its underexpression. This underexpression, in turn, impacts the PI3K/AKT/mTOR pathway, thereby influencing crucial mechanisms like proliferation and apoptosis, playing an important role in the initiation and progression of prostate cancer (PCa). Thus, we aimed to systematically reviewed available information concerning the regulation of PTEN mediated by miRNA in PCa. Electronic databases were searched to identify studies assessing PTEN regulation via PCa miRNAs, the search included combination of the words microRNAs, PTEN and prostatic neoplasms. The quality assessment of the articles included was carried out using an adapted version of SYRCLE and CASP tool. We included 39 articles that measured the relative gene expression of miRNAs in PCa and their relationship with PTEN regulation. A total of 42 miRNAs were reported involved in the development and progression of PCa via PTEN dysregulation (34 miRNAs up-regulated and eight miRNAs down-regulated). Sixteen miRNAs were shown as the principal regulators for genetic interactions leading to carcinogenesis, being the miR-21 the most reported in PCa associated with PTEN down-regulation. We showed the silencing of PTEN could be promoted by a loop between miR-200b and DNMT1 or by direct targeting of PTEN by microRNAs, leading to the constitutive activation of PI3K/AKT/mTOR and interactions with intermediary genes support apoptosis inhibition, proliferation, invasion, and metastasis in PCa. According to our review, dysregulation of PTEN mediated mainly by miR-21, -20a, -20b, -93, -106a, and -106b up-regulation has a central role in PCa development and could be potential biomarkers for diagnosis, prognostic, and therapeutic targets.

Background: Aging is the strongest risk factor for prostate cancer (PCa). It is accompanied by progressive epigenomic divergence, known as epigenetic drift, particularly affecting DNA methylation at regulatory regions. However, the extent to which age-associated promoter methylation contributes to coordinated microRNA (miRNA) expression changes in PCa remains incompletely characterized. Methods: We conducted an integrative in silico analysis of 449 primary tumors from the TCGA-PRAD cohort. Age was modeled as a continuous variable. Age-related miRNA expression changes were estimated from miRNA-seq data using DESeq2. Promoter DNA methylation changes (±2 kb from transcription start sites) were assessed using Illumina 450K arrays and linear regression. MiRNAs showing significant age-associated alterations at both expression and methylation levels were classified as concordant or discordant based on directionality and prioritized using an effect size-based concordance score. We analyzed experimentally validated targets of prioritized miRNAs through functional enrichment and network-based approaches to identify convergent regulatory pathways. Results: Initially, we identified 105 age-associated miRNAs. After filtering, 65 candidates remained. Of these, we found 37 miRNAs with significant age-associated changes at both layers, including 20 concordant and 17 discordant miRNAs. These comprised well-characterized cancer-associated miRNAs and lesser-studied candidates enriched in CpG-rich regulatory regions. Network analyses revealed a limited set of genes under convergent regulation by multiple age-associated miRNAs. These implicated pathways are related to cell cycle control, apoptosis, stress response, and epigenetic regulation. Conclusions: Our findings support a model in which age-dependent promoter methylation drift contributes to coordinated miRNA deregulation in PCa. This convergence highlights biologically plausible miRNA biomarkers and age-sensitive epigenetic circuits relevant to prostate carcinogenesis.

Breast cancer (BCa) is one of the leading causes of death in women with these types of malignancies. Early detection is pivotal to improve prognosis and reduce mortality. Several proteins and genes have been proposed as biomarkers for cancer; however, further studies are required before a molecule is accepted as a definitive biomarker. This study was aimed at investigating the expression of survivin variants S-WT, S-2B, and S-ΔEx3, as well as adipokines LEP and ADIPOQ in breast cancer. Breast samples were obtained from patients with ( ) and without ( ) BCa, and relative gene expression was assessed by RT-qPCR. S-WT and S-2B showed a significant increase in BCa samples ( and , respectively) and in high-aggressiveness BCa ( and , respectively). Despite S-ΔEx3 expression remained globally unchanged, when dividing BCa samples according to the stage, this gene showed a significant tendency to increase towards more advanced stages, and the exact opposite effect was observed for LEP. Furthermore, LEP expression showed a negative correlation with S-2B ( ) and S-WT ( ), and in the same manner, ADIPOQ was negatively related with these two survivin variants ( and , respectively). Interestingly, S-ΔEx3 expression appears unaffected by LEP and ADIPOQ expressions. Our results highlight the importance of investigating specific variants of a given gene, as sequence variation may grant different correlation with other important structures and diseases.

Prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide and the most frequent cancer among men in Mexico, with Sinaloa reporting the highest incidence (GLOBOCAN 2022). PCa arises from uncontrolled proliferation of malignant prostate cells, with multiple contributing factors including genetic alterations such as mutations in the tumor suppressor gene PTEN, a key regulator of the PI3K/AKT pathway. Through a systematic literature review and bioinformatics analysis (NCBI, PDB, UniProt, UCSF Chimera, WinCoot, Mutation3D, SNPs&GO, I-Mutant 2.0, PyMOL 3.0), 30 PTEN mutations associated with PCa were identified. Among these, D107Y, R130Y, and R335H were selected for in silico structural and functional analysis due to their predicted deleterious effects and significant structural changes. Structural modeling confirmed high-quality PTEN models, while Mutation3D and PyMOL analyses revealed that R130Y and R335H induce alterations in bond formation and tertiary structure, potentially affecting phosphatase activity and membrane anchoring. SNP-based predictions suggest that all three mutations may impair PTEN function, although experimental validation is required. These findings highlight the potential impact of specific PTEN mutations on protein stability and function in PCa and propose these variants as targets for future in vitro studies to explore their utility as molecular markers for diagnosis.

Prostate cancer (PCa) represents a significant cause of cancer-associated mortality in the male population worldwide and constitutes a multifactorial disease influenced by genetic and epigenetic factors. Deregulation of genes such as AR and PTEN, as well as alteration in the expression of microRNAs (miRNAs), including miR-145-5p and miR-148b-3p, has been observed in this pathology. This study aimed to explore the correlation between the expression of miR-145-5p, miR-148b-3p, and PTEN in prostate tissue, providing initial insight into their potential interaction in cancer biology. We analyzed 71 samples, comprising 41 from patients with confirmed prostate cancer (PCa group) and 30 from patients with benign prostatic disease (BPD group). Our findings demonstrated a statistically significant association between both miRNAs and the PTEN gene, specifically between miR-148b-3p and PTEN (p = 0.00001) and between miR-145-5p and PTEN (p = 0.0078). These findings support the hypothesis that reduced levels of these miRNAs may be linked to PTEN regulation in prostate pathologies and underscore their potential relevance in PCa biology.

Background/Objectives: Catalase (CAT) plays a pivotal role in cellular redox homeostasis by catalyzing the decomposition of hydrogen peroxide, thereby mitigating oxidative damage. Impaired CAT function has been linked to chronic inflammation, deregulated cell proliferation, and oncogenesis. While numerous CAT variants have been reported, their functional relevance in prostate cancer (PCa) remains unclear. This study investi-gated CAT genetic variants, enzymatic activity, and potential pathogenic significance in PCa. Methods: Peripheral blood samples from 17 patients with prostate cancer (PCa) and 17 patients with benign prostatic hyperplasia (BPH) were processed for genomic DNA extraction and quantification. Reported missense variants were screened using pub-lic genomic databases. Pathogenicity was predicted with SNPs&GO, PolyPhen-2, and I-Mutant 2.0. Protein modeling was performed with UCSF Chimera, and structural quality was assessed via Ramachandran plots. Two selected variants (L299F, A333T) were geno-typed using the rhAmp™ SNP assay. Serum CAT activity was quantified spectrophoto-metrically (240 nm) following Aebi’s protocol. Results: CAT activity was significantly re-duced in PCa compared to BPH (1.44 ± 0.24 vs. 1.91 ± 0.25 U/mg protein, p = 0.033), with no association to age, PSA levels, or comorbidities. In silico predictions identified variants K177T, G216V, and L351P as potentially deleterious, while N452S appeared benign. Gen-otyping revealed that all participants were wild-type homozygous for L299F and A333T. Conclusions: PCa is characterized by diminished CAT activity independent of the inves-tigated variants, suggesting an alternative regulatory mechanism, such as epigenetic reg-ulation or post-translational modifications, may drive CAT downregulation. These find-ings support further investigation into CAT as a potential biomarker and therapeutic tar-get in oxidative stress–mediated prostate carcinogenesis.