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Canine mammary tumors (CMTs) are one of the most common neoplasms in female dogs. Unfortunately, the current diagnosis often occurs in later stages, and there is a pressing need for more comprehensive data on treatment options to improve overall prognosis. Consequently, the early detection of these tumors is critical for improving treatment outcomes and survival rates. As such, biomarkers are essential for improving the diagnosis, treatment, and prognosis of CMT, the reason for which further research is required to enhance our understanding of the disease. The most studied biomarkers for CMT are evaluated from serum and tissue samples using different molecular approaches and relate to proliferation and cell cycle. Several biomarkers were also described regarding cell damage, autophagy and apoptotic-related pathways, hypoxia, angiogenesis, EMT, invasion, metastasis or cancer stem features. Overall, biomarkers have shown the potential to be used as a tool for the early detection of mammary tumors in dogs. However, more research is needed to validate these biomarkers and to develop sensitive and specific diagnostic tests. In this regard, we aimed to review known biomarkers and their role in CMT comprehensively. We also encouraged further investigations of reliable biomarkers that could improve treatment outcomes and survival rates for dogs with this disease.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that may function as tumor suppressors or oncogenes. Alteration of their expression levels has been linked to a range of human malignancies, including cancer. The objective of this investigation is to assess the relative expression levels of certain miRNAs to distinguish between prostate cancer (PCa) from benign prostatic hyperplasia (BPH). Blood plasma was collected from 66 patients diagnosed with BPH and 58 patients with PCa. Real-time PCR technology was used to evaluate the relative expression among the two groups for miR-106a-5p and miR-148a-3p. The significant downregulation of both miRNAs in plasma from PCa versus BPH patients suggests their potential utility as diagnostic biomarkers for distinguishing between these conditions. The concurrent utilization of these two miRNAs slightly enhanced the sensitivity for discrimination among the two analyzed groups, as shown in ROC curve analysis. Further validation of these miRNAs in larger patient cohorts and across different stages of PCa may strengthen their candidacy as clinically relevant biomarkers for diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Canine mammary tumors (CMTs) represent a prevalent malignancy in female dogs. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression and are implicated in various cancer types, including CMTs. This study aimed to investigate the altered miRNA expression patterns in CMTs and their potential role in tumorigenesis. We analyzed miRNA profiles in a cohort of CMT samples and matched normal tissues using a custom canine panel microarray slide (Agilent technology). The bioinformatics analysis overlapped the altered miRNA signature in CMT with human breast cancer miRNA (TCGA patient cohort). The biological significance of this altered miRNA signature was evaluated using Ingenuity Pathway Analysis. Our results revealed a distinctive miRNA expression signature associated with CMTs compared to normal mammary tissues, and when overlapped with human breast cancer miRNA data (TCGA cohort), we identified a common signature composed of one overexpressed transcript and eight downregulated transcripts. In conclusion, our study provides comprehensive insights into the altered miRNA expression patterns in CMTs, shedding light on their potential contribution to the pathogenesis of these tumors. Further investigation into the specific roles of these dysregulated miRNAs is warranted to elucidate their precise involvement in CMT progression and to explore their therapeutic implications. [ABSTRACT FROM AUTHOR]

Recent research has revealed the importance of miRNAs in the diagnosis and clinical evolution of papillary thyroid cancer (PTC). We aim to identify a specific miRNA profile that could differentiate between specific subtypes of PTC. Methods: In this cross-sectional study, total RNA was extracted from paraffin-embedded tissues of 43 patients, 17 with an infiltrative follicular variant of PTC (iFVPTC) and 26 with a conventional variant of PTC (cPTC). Nine miRNAs were evaluated using qRT-PCR technology and specific miRNA assays. Results: We found specific patterns for cPTC and iFVPTC, such as miRNA altered in both types of tumours (miR-146b-5p, miR-181a-5p, miR-221-3p, miR-21-5p and miR-222-3p) and two miRNAs significantly expressed only in cPTC (miR-20b-5p, miR-21-5p). The iFVPTC group presented strong and moderate correlations between miRNA expression and clinical data. miR-221-3p, miR-195-5p, miR-181-5p, miR-146b-5p and miR-222 were correlated with age, tumour size (TS) or lymph node metastases (N), while only miR-20b-5p, miR-195-5p and miR-181-5p were correlated with TS, N and age in the cPTC group. Conclusions: The present study allowed the identification of a signature of two miRNAs to confirm miRNA differences between the two histological subtypes of TC. Our results provide advances in the molecular diagnosis of TC and could help to improve the diagnostic performance of already existing molecular classifiers. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a primary brain tumor arising from glial cells. The tumor is highly aggressive, the reason for which it has become the deadliest brain tumor type with the poorest prognosis. Like other cancers, it compromises molecular alteration on genetic and epigenetic levels. Epigenetics refers to changes in gene expression or cellular phenotype without the occurrence of any genetic mutations or DNA sequence alterations in the driver tumor-related genes. These epigenetic changes are reversible, making them convenient targets in cancer therapy. Therefore, we aim to review critical epigenetic dysregulation processes in glioblastoma. We will highlight the significant affected tumor-related pathways and their outcomes, such as regulation of cell cycle progression, cell growth, apoptosis, angiogenesis, cell invasiveness, immune evasion, or acquirement of drug resistance. Examples of molecular changes induced by epigenetic modifications, such as DNA epigenetic alterations, histone post-translational modifications (PTMs), and non-coding RNA (ncRNA) regulation, are highlighted. As understanding the role of epigenetic regulators and underlying molecular mechanisms in the overall pro-tumorigenic landscape of glioblastoma is essential, this literature study will provide valuable insights for establishing the prognostic or diagnostic value of various non-coding transcripts, including miRNAs. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have gained recent attraction due to their functional versatility and particular structure connected to human diseases. Current investigations are focused on the interplay between their ability to sponge smaller species of RNAs, such as microRNAs (miRNAs), thus influencing their regulatory activity on gene expression and protein templates. Therefore, their reported implication in various biological processes axis has resulted in an accumulating number of studies. While the testing and annotation methods of novel circular transcripts are still under development, there is still a plethora of transcript candidates suitable for investigation in human disease. The discordance in the literature regarding the approaches used in circRNAs quantification and validation methods, especially regarding qRT-PCR, the current golden standard procedure, leads to high result variability and undermines the replicability of the studies. Therefore, our study will offer several valuable insights into bioinformatic data for experimental design for circRNA investigation and in vitro aspects. Specifically, we will highlight key aspects such as circRNA database annotation divergent primer design and several processing steps, such as RNAse R treatment optimization and circRNA enrichment assessment. Additionally, we will provide insights into the exploration of circRNA-miRNA interactions, a prerequisite for further functional investigations. With this, we aim to contribute to the methodological consensus in a currently expanding field with possible implications for assessing therapeutic targets and biomarker discovery. [ABSTRACT FROM AUTHOR]

The lack of estrogen or progesterone receptors and absence of HER2 amplification/overexpression in triple-negative breast cancer (TNBC) restricts therapeutic options used in clinical management. MicroRNAs (miRNAs) are small, non-coding transcripts which affect important cellular mechanisms by regulating gene expression at the post-transcriptional level. Among this class, attention was focused on miR-29b-3p with a high profile in TNBC and correlated with the overall survival rates, as TCGA data revealed. This study aims to investigate the implication of the miR-29b-3p inhibitor in TNBC cell lines by identifying a potential therapeutic transcript, improving the clinical outcomes of this disease. The experiments were performed on two TNBC cell lines (MDA-MB-231 and BT549) as in vitro models. An established dose of 50 nM was used for all functional assays performed on the miR-29b-3p inhibitor. A decreased level of miR-29b-3p determined a significant reduction in cell proliferation and colony-forming capacity. At the same time, the changes occurring at the molecular and cellular levels were highlighted. We observed that, when inhibiting the expression level of miR-29b-3p, processes such as apoptosis and autophagy were activated. Further, microarray data revealed that the miRNA expression pattern was altered after miR-29b-3p inhibition, pointing out 8 overexpressed and 11 downregulated miRNAs specific for BT549 cells and 33 upregulated and 10 downregulated miRNAs that were specific for MDA-MB-231 cells. As a common signature for both cell lines, three transcripts were observed, two downregulated, miR-29b-3p and miR-29a, and one upregulated, miR-1229-5p. According to DIANA miRPath, the main predicted targets are related to ECM (extracellular matrix) receptor interaction and TP53 signaling. An additional validation step through qRT-PCR was performed, which showed an upregulation of MCL1 and TGFB1. By inhibiting the expression level of miR-29b-3p, it was shown that complex regulatory pathways targeted this transcript in TNBC cells. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is still one of the types of cancer with the highest death rates. MicroRNAs (miRNAs) play essential roles in NSCLC development. This study evaluates miRNA expression patterns and specific mechanisms in male patients with NSCLC. Methods: We report an integrated microarray analysis of miRNAs for eight matched samples of males with NSCLC compared to the study of public datasets of males with NSCLC from TCGA, followed by qRT-PCR validation. Results: For the TCGA dataset, we identified 385 overexpressed and 75 underexpressed miRNAs. Our cohort identified 54 overexpressed and 77 underexpressed miRNAs, considering a fold-change (FC) of ±1.5 and p < 0.05 as the cutoff value. The common miRNA signature consisted of eight overexpressed and nine underexpressed miRNAs. Validation was performed using qRT-PCR on the tissue samples for miR-183-3p and miR-34c-5p and on plasma samples for miR-34c-5p. We also created mRNA-miRNA regulatory networks to identify critical molecules, revealing NSCLC signaling pathways related to underexpressed and overexpressed transcripts. The genes targeted by these transcripts were correlated with overall survival. Conclusions: miRNAs and some of their target genes could play essential roles in investigating the mechanisms involved in NSCLC evolution and provide opportunities to identify potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Infertility is an important health concern worldwide. Although lifestyle habits and behaviors have been widely reported as predictors of IVF outcomes by previous studies, they have not been reported for Romanian women undergoing IVF. In this regard, our pilot study aimed to begin to address the data gap by assessing lifestyle predictors of in vitro fertilization (IVF) outcomes in Romanian women. Study design: Our pilot study included 35 participants who completed a first IVF cycle at a single infertility center. We evaluated individual self-reported lifestyle habits and behaviors as predictors of IVF outcomes, and employed principal component analysis (PCA) to characterize multiple lifestyle habits and behaviors into personal care product (PCP) use, and healthy diet and physical activity patterns as predictors of IVF outcomes. Results: Our PCA analysis showed that greater use of PCPs was associated with lower probabilities of pregnancy (RR: 0.92, 95% CI [0.87-0.98]) and live birth (RR: 0.94, 95% CI [0.88-1.01]) while, the healthy dietary habits and physical activity were associated with a higher likelihood of pregnancy, although without statistical significance (RR: 1.10, 95% CI [0.93-1.30]). Conclusions: In this pilot study we identified associations between IVF outcomes among Romanian women and certain lifestyle habits and behaviors including stress, diet and physical activity, and certain PCP use. We also estimated the joint effects of multiple lifestyle factors using PCA and found that PCP use, healthy dietary habits and physical activity were associated with IVF outcomes. [ABSTRACT FROM AUTHOR]

Despite the great progress in its early diagnosis and treatment, colon adenocarcinoma (COAD) is still poses important issues to clinical management. Therefore, the identification of novel biomarkers or therapeutic targets for this disease is important. Using UALCAN, the top 25 upregulated and downregulated genes in COAD were identified. Then, a Kaplan–Meier plotter was employed for these genes for survival analysis, revealing the correlation with overall survival rate only for MMP3 (Matrix Metallopeptidase 3) and TESC (Tescalcin). Despite this, the mRNA expression levels were not correlated with the tumor stages or nodal metastatic status. MMP3 and TESC are relevant targets in COAD that should be additionally validated as biomarkers for early diagnosis and prevention. Ingenuity Pathway Analysis revealed the top relevant network linked to Post-Translational Modification, Protein Degradation, and Protein Synthesis, where MMP3 was at the core of the network. Another important network was related to cell cycle regulation, TESC being a component of this. We should also not underestimate the complex regulatory mechanisms mediated by the interplay of the multiple other regulatory molecules, emphasizing the interconnection with molecules related to invasion and migration involved in COAD, that might serve as the basis for the development of new biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a common mycotoxin that contaminates cereals and their by-products. The gastrointestinal tract is the first physical barrier against ingested food contaminants. DON contributes to the loss of barrier function of the intestine through the decreased expression of claudin-4 protein, a tight junction protein. The mechanism by which DON alters the intestinal barrier function remains poorly characterized. Therefore, we investigated the involvement of mitogen-activated protein kinases (MAPK) in the DON-induced loss of barrier function. We first verified that 30 [micro]mol/L of DON activated MAPK in a highly sensitive porcine intestinal epithelial cell line (IPEC-1). Inhibition of p44/42 extracellular signal-regulated kinase (ERK) phosphorylation, with 0.5 [micro]mol/L of the specific MAPK pharmacological inhibitor U0126 for 2 h, restored the barrier function of the differentiated intestinal epithelial cell monolayers. The restoration of barrier function was evaluated by trans-epithelial electrical resistance measurements and tracer flux paracellular permeability experiments. The U0126 also restored the intestinal expression of claudin-4 protein, thereby demonstrating that MAPK activation is involved in claudin-4 protein expression and claudin-4 is involved in the maintenance of the intestinal epithelial cell barrier function. Further experiments indicated that p44/42 ERK is not involved in the transcriptional regulation of claudin-4. In conclusion, we demonstrated that DON-induced activation of the p44/42 ERK signaling pathway inhibits the expression of claudin-4 protein, which leads to impaired intestinal barrier function. Given the high levels of DON in cereal grains, these observations of impaired barrier function have implications for human and animal health. J. Nutr. 140: 1956-1962, 2010. doi: 10.3945/jn.110.123919.

Background: Cervical cancer is one of the most common malignancies in women in terms of prevalence and mortality. Cervical cancer has some particularities that distinguish it from any other oncologic pathology: first, it is completely preventable by prompt detection of its precursor, cervical intraepithelial neoplasia (CIN); second, the Human Papillomavirus (HPV) infection is a known etiological agent; third, the mean age at diagnosis is much lower than in other oncologic conditions, as a consequence of the sexually-transmitted HPV. Methods: We evaluated the expression level of several long noncoding RNAs and a microRNA in samples from 30 patients with CIN, 9 with cervical cancer and 38 normal samples using qRT-PCR technology. Results: We observed higher expression levels for MEG3, DAPK1, MLH1 and MALAT1 in CIN samples than in normal samples, whereas TIMP3 and SOX1 had lower expression levels. For cancer samples, DAPK1, MLH1 and MALAT1 had higher expression, and MEG3, TIMP3 and SOX1 had lower expression when compared to normal samples. In the case of CIN versus cancer samples, only MEG3 gene showed a statistically significant difference. The expression of miR-205-5p was lower in both CIN and cancer samples compared to normal samples. Conclusion: Decreased MEG3 expression could be considered an alarm signal in the transition from a premalignant cervical lesion to invasive cancer, while altered expression levels of TIMP3, SOX1, MLH1, MALAT1 and miR-205-5p could serve as early biomarkers in the diagnosis of premalignant cervical lesions. Future studies, including a larger number of patients with CIN, will be of particular importance in validating these observations. [ABSTRACT FROM AUTHOR]

Lung cancers are broadly divided into two categories: non-small-cell lung carcinoma (NSCLC), which accounts for 80–85% of all cancer cases, and small-cell lung carcinoma (SCLC), which covers the remaining 10–15%. Recent advances in cancer biology and genomics research have allowed an in-depth characterization of lung cancers that have revealed new therapy targets (EGFR, ALK, ROS, and KRAS mutations) and have the potential of revealing even more biomarkers for diagnostic, prognostic, and targeted therapies. A new source of biomarkers is represented by non-coding RNAs, especially microRNAs (miRNAs). MiRNAs are short non-coding RNA sequences that have essential regulatory roles in multiple cancers. Therefore, we aim to investigate the tumor microenvironment (TME) and miRNA tumor profile in a subset of 51 early-stage lung cancer samples (T1 and T2) to better understand early tumor and TME organization and molecular dysregulation. We analyzed the immunohistochemistry expression of CD4 and CD8 as markers of the main TME immune populations, E-cadherin to evaluate early-stage epithelial-to-mesenchymal transition (EMT), and p53, the main altered tumor suppressor gene in lung cancer. Starting from these 4 markers, we identified and validated 4 miRNAs that target TP53 and regulate EMT that can be further investigated as potential early-stage lung cancer biomarkers. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is currently associated with a lack of treatment options. Arsenic derivatives have shown antitumoral activity both in vitro and in vivo; however, their mode of action is not completely understood. In this work we evaluate the response to arsenate of the double positive MCF-7 breast cancer cell line as well as of two different TNBC cell lines, Hs578T and MDA-MB-231. Multimodal experiments were conducted to this end, using functional assays and microarrays. Arsenate was found to induce cytoskeletal alteration, autophagy and apoptosis in TNBC cells, and moderate effects in MCF-7 cells. Gene expression analysis showed that the TNBC cell lines' response to arsenate was more prominent in the G2M checkpoint, autophagy and apoptosis compared to the Human Mammary Epithelial Cells (HMEC) and MCF-7 cell lines. We confirmed the downregulation of anti-apoptotic genes (MCL1, BCL2, TGFβ1 and CCND1) by qRT-PCR, and on the protein level, for TGFβ2, by ELISA. Insight into the mode of action of arsenate in TNBC cell lines it is provided, and we concluded that TNBC and non-TNBC cell lines reacted differently to arsenate treatment in this particular experimental setup. We suggest the future research of arsenate as a treatment strategy against TNBC. [ABSTRACT FROM AUTHOR]

Oral cancer is one of the leading causes of death worldwide, with a reported 5-year survival rate of around 50% after treatment. Epigenetic modifications are considered to have a key role in oral carcinogenesis due to histone modifications, aberrant DNA methylation, and altered expression of miRNAs. MicroRNAs (miRNAs) are small non-coding RNAs that have a key role in cancer development by regulating signaling pathways involved in carcinogenesis. MiRNA deregulation identified in oral cancer has led to the idea of using them as potential biomarkers for early diagnosis, prognosis, and the development of novel therapeutic strategies. In recent years, a key role has been observed for risk factors in preventing and treating this malignancy. The purpose of this review is to summarize the recent knowledge about the altered mechanisms of oral cancer due to risk factors and the role of miRNAs in these mechanisms. [ABSTRACT FROM AUTHOR]

Background: Lung cancer remains one of the most diagnosed malignancies, being the second most diagnosed cancer, while still being the leading cause of cancer-related deaths. Late diagnosis remains a problem, alongside the high mutational burden encountered in lung cancer. Methods: We assessed the genetic profile of cancer genes in lung cancer using The Cancer Genome Atlas (TCGA) datasets for mutations and validated the results in a separate cohort of 32 lung cancer patients using tumor tissue and whole blood samples for next-generation sequencing (NGS) experiments. Another separate cohort of 32 patients was analyzed to validate some of the molecular alterations depicted in the NGS experiment. Results: In the TCGA analysis, we identified the most commonly mutated genes in each lung cancer dataset, with differences among the three histotypes analyzed. NGS analysis revealed TP53, CSF1R, PIK3CA, FLT3, ERBB4, and KDR as being the genes most frequently mutated. We validated the c.1621A>C mutation in KIT. The correlation analysis indicated negative correlation between adenocarcinoma and altered PIK3CA (r = −0.50918; p = 0.0029). TCGA survival analysis indicated that NRAS and IDH2 (LUAD), STK11 and TP53 (LUSC), and T53 (SCLC) alterations are correlated with the survival of patients. Conclusions: The study revealed differences in the mutational landscape of lung cancer histotypes. [ABSTRACT FROM AUTHOR]