Search Results (3)

Background: Mesoporous titanium dioxide nanoparticles (mTiNPs) are known for their chemical stability, non-toxicity, antimicrobial and anticancer effects, as well as for their photocatalytic properties. When this material is subjected to UV radiation, its electronic structure shifts, and during that process, reactive oxygen species are generated, which in turn exert apoptotic events on the cancer cells. Objectives: We evaluated the cytotoxic effects of UV-irradiated mTiNPs on prostate cancer (PCa) cell line PC3 with the aim of demonstrating that the interaction between UV-light and mTiNPs positively impacts the nanomaterial’s cytotoxic efficiency. Moreover, we assessed the differential expression of key oncomiRs and tumor suppressor (TS) miRNAs, as well as their associated target genes, in cells undergoing this treatment. Methods: PBS-suspended mTiNPs exposed to 290 nm UV light were added at different concentrations to PC3 cells. Cell viability was determined after 24 h with a crystal violet assay. Then, the obtained IC₅₀ concentration of UV-nanomaterial was applied to a new PC3 cell culture, and the expression of a set of miRNAs and selected target genes was evaluated via qRT-PCR. Results: The cells exposed to photo-activated mTiNPs required 4.38 times less concentration of the nanomaterial than the group exposed to non-irradiated mTiNPs to achieve the half-maximal inhibition, demonstrating an improved cytotoxic performance of the UV-irradiated mTiNPs. Moreover, the expression of miR-18a-5p, miR-21-5p, and miR-221-5p was downregulated after the application of UV-mTiNPs, while TS miR-200a-5p and miR-200b-5p displayed an upregulated expression. Among the miRNA target genes, PTEN was found to be upregulated after the treatment, while BCL-2 and TP53 were underexpressed. Conclusions: Our cytotoxic outcomes coincided with previous reports performed in other cancer cell lines, strongly suggesting UV-irradiated mTiNPs as a promising nano-therapeutic approach against PCa. On the other hand, to the best of our knowledge, this is the first report exploring the impact of UV-irradiated mTiNPs on key onco- and TS microRNAs in PCa cells. Full article

Background: Triple-negative breast cancer (TNBC) and High-Grade Serous Ovarian Cancer (HGSOC) are aggressive malignancies that share similarities; however, different ages of onset may reflect distinct tumor behaviors. Thus, our aim was to compare somatic mutations in potential driver genes in 109 TNBC and 81 HGSOC from young (Y ≤ 40 years) and elderly (E ≥ 75 years) patients. Methods: Open access mutational data (WGS or WES) were collected for TNBC and HGSOC patients. Potential driver genes were those that were present in the Cancer Gene Census—CGC, the Candidate Cancer Gene Database—CCGD, or OncoKB and those that were considered pathogenic in variant effect prediction tools. Results: Mutational signature 3 (homologous repair defects) was the only gene that was represented in all four subgroups. The median number of mutated CGCs per sample was similar in HGSOC (Y:3 vs. E:4), but it was higher in elderly TNBC than it was in young TNBC (Y:3 vs. E:6). At least 90% of the samples from TNBC and HGSOC from Y and E patients presented at least one known affected TSG. Besides TP53, which was mutated in 67–83% of the samples, the affected TSG in TP53 wild-type samples were NF1 (yHGSOC and yTNBC), PHF6 (eHGSOC and yTNBC), PTEN, PIK3R1 and ZHFX3 (yTNBC), KMT2C, ARID1B, TBX3, and ATM (eTNBC). A few samples only presented one affected oncogene (but no TSG): KRAS and TSHR in eHGSOC and RAC1 and PREX2 (a regulator of RAC1) in yTNBC. At least ⅔ of the tumors presented mutated oncogenes associated with tumor suppressor genes; the Ras and/or PIK3CA signaling pathways were altered in 15% HGSOC and 20–35% TNBC (Y vs. E); DNA repair genes were mutated in 19–33% of the HGSOC tumors but were more frequently mutated in E-TNBC (56%). However, in HGSOC, 9.5% and 3.3% of the young and elderly patients, respectively, did not present any tumors with an affected CGC nor did 4.65% and none of the young and elderly TNBC patients. Conclusion: Most HGSOC and TNBC from young and elderly patients present an affected TSG, mainly TP53, as well as mutational signature 3; however, a few tumors only present an affected oncogene or no affected cancer-causing genes. Full article

The PTEN onco-suppressor gene is likely to play an important role in the onset of brain cancer, namely glioblastoma multiforme. Consequently, the PTEN regulatory network, involving microRNAs and competitive endogenous RNAs, becomes a crucial tool for understanding the mechanism related to low levels of expression in cancer patients. This paper introduces a novel model for the regulation of PTEN whose solution is approximated by a high-dimensional system of ordinary differential equations under the assumption that the Law of Mass Action applies. Extensive numerical simulations are presented that mirror parts of the biological subtext that lies behind various alterations. Given the complexity of processes involved in the acquisition of empirical data, initial conditions and reaction rates were inferred from the literature. Despite this, the proposed model is shown to be capable of capturing biologically reasonable behaviors of inter-species interactions, thus representing a positive result, which encourages pursuing the possibility of experimenting on data hopefully provided by omics disciplines. Full article