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Nuclear factor kappa B (NF-κB) signaling plays a central role in inflammation, immunity, cell survival, and cancer progression. Its constitutive activation is frequently observed in breast cancer, contributing to tumor growth, treatment resistance, and metastasis. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and may modulate NF-κB signaling in a subtype-specific or -independent manner. The aim of the study was to identify miRNAs that may potentially regulate the activity of genes associated with NF-κB signaling across five molecular subtypes of breast cancer in Polish women. Tumor and matched normal tissue samples were collected from 405 patients with five breast cancer subtypes: luminal A (n = 130), HER2-negative luminal B (n = 100), HER2-positive luminal B (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (TNBC, n = 43). Expression profile of selected NF-κB-related genes were evaluated using mRNA microarrays and RT-qPCR. Protein levels were assessed by ELISA. Candidate regulatory miRNAs were identified via miRNA microarrays and validated using the miRDB database. A consistent upregulation of MAP3K7, TAB2, TNFAIP3, CSNK2A1, BCL2L1, XIAP, CXCL2, and PLAU was observed across all subtypes, suggesting activation of canonical NF-κB signaling. Downregulation of specific miRNAs, miR-1297 and miR-30a (targeting MAP3K7), miR-134 (TAB2), miR-125b (TNFAIP3), and miR-4329 (XIAP), may contribute to this deregulation. For CSNK2A1, BCL2L1, CXCL2, and PLAU, no regulatory miRNAs meeting our criteria were identified. Our study reveals a subtype-independent activation of the canonical NF-κB signaling pathway in breast cancer, underpinned by consistent upregulation of key components (at both the transcript and protein levels. Dysregulation of specific miRNAs likely contributes to this altered gene expression. These findings suggest the presence of a common NF-κB-driven oncogenic program across molecular subtypes, with potential implications for developing miRNA-based therapeutic strategies targeting inflammation, survival signaling, and treatment resistance in breast cancer.

Pancreatic cancer is a disease with an extremely poor prognosis. Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a proapoptotic stress-induced p53 target gene. In this article, we show by immunohistochemical analysis that TP53INP1 expression is dramatically reduced in pancreatic ductal adenocarcinoma (PDAC) and this decrease occurs early during pancreatic cancer development. TP53INP1 reexpression in the pancreatic cancer-derived cell line MiaPaCa2 strongly reduced its capacity to form s.c., i.p., and intrapancreatic tumors in nude mice. This anti-tumoral capacity is, at least in part, due to the induction of caspase 3-mediated apoptosis. In addition, TP53INP1⁻/⁻ mouse embryonic fibroblasts (MEFs) transformed with a retrovirus expressing E1A/rasV¹² oncoproteins developed bigger tumors than TP53INP1⁺/⁺ transformed MEFs or TP53INP1⁻/⁻ transformed MEFs with restored TP53INP1 expression. Finally, TP53INP1 expression is repressed by the oncogenic micro RNA miR-155, which is overexpressed in PDAC cells. TP53INP1 is a previously unknown miR-155 target presenting anti-tumoral activity.

Background The global HIV prevalence estimate at the end of 2022 was 39 million. This has led to mass testing to diagnose new cases, and the conduction of prognostic tests for monitoring HIV progression. This is being done to meet the targets of the 95%: 95%: 95% UN AIDS goal which is to be achieved by 2025. Therefore, there is the need to discover other diagnostic and prognostic biomarkers to be supplemented with the currently used ones. Studies indicate that micro RNAs have their levels influenced by the presence and replication of aetiologic agents, thus the micro RNA (miRNA) expression profile test may serve the dual purpose of HIV diagnosis and prognosis. Therefore, this study assessed the HIV-1 diagnostic and prognostic potential of the expression patterns of circulating miRNAs in HIV positive persons in Cape Coast, Ghana. Methods A cross-sectional research design was used to assess the expression patterns of seven miRNAs – hsa-mir-146a, hsa-mir-155, hsa-mir-34a, hsa-mir-29a, hsa-mir-29b, hsa-mir-223 and hsa-mir-27a in 72 plasma samples. The samples were obtained from six antiretroviral therapy naïve persons, 37 ART-experienced persons and 29 healthy controls. Total RNA was extracted, afterwards, cDNA synthesis and RT-qPCR was done. Results There were low levels of hsa-mir-155, and elevated levels of two miRNAs – hsa-mir-34a, and hsa-mir-27a in ART-experienced persons relative to healthy control. The sensitivities of the above miRNAs were 82.14%, 72.73% and 81.25 respectively, and specificities were 86.21%, 70.59% and 87.50% respectively. Upregulated levels of hsa-mir-223 was associated with HIV-1 infection in ART-naïve persons. Hsa-mir-223, hsa-mir-155, hsa-mir-29a and hsa-mir29b were present in quantities that distinguished between viral load categories classified as very low and high. These miRNAs were correlated with viral load. Low levels of hsa-mir-155 in HIV-1 persons with viral load of less than 7cps/ml distinguished them from HIV-negative control. Increased levels of hsa-mir-146a correlated with ART-resistance. Conclusion Decreased levels of hsa-mir-155, and elevated levels of hsa-mir-34a, hsa-mir-223 and hsa-mir-27a could be biomarkers of HIV-1. Hsa-mir-155, hsa-mir-29a, hsa-mir29b and hsa-mir-223 could be good biomarkers of HIV-1 progression and Low levels of hsa-mir-155 may possess the potential to detect minute HIV-1 RNA copies. Elevated levels of hsa-mir-146a could be a potential biomarker of ART-resistance.

Osteoporosis is a major concern worldwide and can be attributed to an imbalance between osteoblastic bone formation and osteoclastic bone resorption due to the natural aging process. Heritable factors account for 60–80% of optimal bone mineralization; however, the finer details of pathogenesis remain to be elucidated. Micro RNA (miRNA) and long-non-coding RNA (lncRNA) are two targets that have recently come into the spotlight due to their ability to control gene expression at the post-transcriptional level and provide epigenetic modification. miRNAs are a class of non-coding RNAs that are approximately 18–25 nucleotides long. It is thought that up to 60% of human protein-coding genes may be regulated by miRNAs. They have been found to regulate gene expression that controls osteoblast-dependent bone formation and osteoclast-related bone remodeling. lncRNAs are highly structured RNA transcripts longer than 200 nucleotides that do not translate into proteins. They have very complex secondary and tertiary structures and the same degradation processes as messenger RNAs. The fact that they have a rapid turnover is due to their sponge function in binding the miRNAs that lead to a degradation of the lncRNA itself. They can act as signaling, decoy, and framework molecules, or as primers. Current evidence suggests that lncRNAs can act as chromatin and transcriptional as well as post-transcriptional regulators. With regards to osteoporosis, lncRNA is thought to be involved in the proliferation, apoptosis, and inflammatory response of the bone. This review, which is based on a systematic appraisal of the current literature, provides current molecular and genetic opinions on the roles of miRNAs and lncRNAs in osteoporosis. Further research into the epigenetic modification and the regulatory roles of these molecules will bring us closer to potential disease-modifying treatment for osteoporosis. However, more issues regarding the detailed actions of miRNAs and lncRNAs in osteoporosis remain unknown and controversial and warrant future investigation.

Background: Vulvar cancer mainly affects postmenopausal women, but its incidence is rising among younger individuals due to persistent HPV infection. Validated diagnostic biomarkers remain lacking, though circulating exosomal microRNAs (exomiRs) have recently emerged as promising liquid biopsy tools across various cancers. Objective: The purpose of this study was to identify a panel of dysregulated plasma-derived extracellular vesicle (EV)-associated miRNAs, hereafter referred to as exosomal micro-RNAs, as liquid biopsy markers for the detection of vulvar cancer and for assessment of HPV-positivity. Methods: Five healthy donor (HD) and 10 vulvar cancer samples underwent Next-Generation Sequencing to screen for differentially expressed exomiRs. The seven most dysregulated and four stably expressed exomiRs were subsequently analyzed in 81 cancer and 60 HD samples by qRT-PCR. Differential expression was determined by the 2−ΔΔCT method. Binary regression was used to construct an exomiR panel. HPV status was assessed using mass spectrometry. Results: Five single exomiRs showed a statistically significant dysregulation in cancer patients compared to healthy controls: miR-143-3p, miR-223-3p, miR-451a, miR-4516 and miR-151a-5p. The combination of six exomiRs resulted in a panel with superior diagnostic ability (p < 0.001; ROC-AUC = 0.805; 95% CI: 0.726–0.884) in distinguishing cancer patients from HDs. A model consisting of miR-223-3p, miR-143-3p and miR-451a could discriminate HPV-positive from -negative (p = 0.003; ROC-AUC = 0.939), and a model of miR-4516, miR-143-3p, miR-16-5p and miR-451a was predictive of lymph node positivity (p < 0.001, ROC-AUC = 0.786). Multivariate Cox regression showed that a model of downregulated miR-16-5p and upregulated miR-451a was significantly associated with poorer survival (p = 0.023). Conclusions: This study indicates the future potential of exomiRs as diagnostic and prognostic liquid biopsy markers for vulvar cancer.

Background Multiple myeloma (MM) accounts for 10% of all hematological malignancies. Dysregulation of microRNAs (miRNAs) or long non-coding RNAs (lncRNAs) has important impacts on progression of MM. Circular RNAs (circRNAs) are correlated with malignancy in the modulation of tumor progression. This study aims to investigate the effect of circ_0000190 on regulating the progression of MM. Method Microscopic examination via single molecule fluorescent in situ hybridization indicates the location of circ_0000190. qRT-PCR and Western blot were used to evaluate the expression of RNAs and proteins. Potential target of circ_0000190 was searched as miRNA, and examined by luciferase reporter assay. A computational screen was also conducted to search the potential target of miRNA. In vitro cell viability, proliferation, apoptosis assays and flow cytometric were performed to assess the effects of circ_0000190 and its target on MM. Mice model of human MM was established with subcutaneous xenograft tumor, qRT-PCR and western blot were performed to detect the underlying mechanisms of circ_0000190 on MM. Results Circ_0000190 was located in the cytoplasm, and down-regulated in both bone marrow tissue and peripheral blood, while the target of circ_0000190, miR-767-5p, was up-regulated, suggesting a negative correlation between them. The binding ability between circ_0000190 and miR-767-5p was confirmed by luciferase reporter assay. Moreover, circ_0000190 inhibited cell viability, proliferation and induced apoptosis of MM thus inhibiting cell progression, which is partially through the negative regulation of miR-767-5p. Mitogen-activated protein kinase 4 (MAPK4) is a direct target of miR-767-5p. In addition, over-expression of miR-767-5p promoted cell progression by directly targeting and regulating MAPK4. The MM model mice with administration of circ_0000190 suppressed tumor growth and progression. Conclusion Our results revealed that the ability of circ_0000190 to protect against MM was inherited through repression of miR-767-5p, and miR-767-5p might be a tumor drive through targeting MAPK4. Therefore, a novel role of circ_0000190 on regulating the progression of MM was found, and the clinical application of circRNAs might represent a strategy in MM.

The keratinocyte carcinomas, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs, assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment.

Neuropathic pain is a widespread clinical issue caused by somatosensory nervous system damage, affecting numerous individuals. It poses considerable economic and public health challenges, and managing it can be challenging due to unclear underlying mechanisms. Nevertheless, emerging evidence suggests that neurogenic inflammation and neuroinflammation play a role in developing pain patterns. Emerging evidence suggests that neurogenic inflammation and neuroinflammation play significant roles in developing neuropathic pain within the nervous system. Increased/decreased miRNA expression patterns could affect the progression of neuropathic and inflammatory pain by controlling nerve regeneration, neuroinflammation, and the expression of abnormal ion channels. However, our limited knowledge of miRNA targets hinders a complete grasp of miRNA’s functions. Meanwhile, exploring exosomal miRNA, a recently uncovered role, has significantly advanced our comprehension of neuropathic pain’s pathophysiology in recent times. In this review, we present a comprehensive overview of the latest miRNA studies and explore the possible ways miRNAs might play a role in the development of neuropathic pain.

Currently, there are very few loss-of-function mutations in micro-RNA genes. Here, we characterize two members of the Arabidopsis MIR159 family, miR159a and miR159b, that are predicted to regulate the expression of a family of seven transcription factors that includes the two redundant GAMYB-like genes, MYB33 and MYB65. Using transfer DNA (T-DNA) insertional mutants, we show that a mir159ab double mutant has pleiotropic morphological defects, including altered growth habit, curled leaves, small siliques, and small seeds. Neither mir159a nor mir159b single mutants displayed any of these traits, indicating functional redundancy. By using reporter-gene constructs, it appears that MIR159a and MIR159b are transcribed almost exclusively in the cells in which MYB33 is repressed, as had been previously determined by comparison of MYB33 and mMYB33 (an miR159-resistant allele of MYB33) expression patterns. Consistent with these overlapping transcriptional domains, MYB33 and MYB65 expression levels were elevated throughout mir159ab plants. By contrast, the other five GAMYB-like family members are transcribed predominantly in tissues where miR159a and miR159b are absent, and consequently their expression levels are not markedly elevated in mir159ab. Additionally, mMYB33 transgenic plants can phenocopy the mir159ab phenotype, suggesting that its phenotype is explained by deregulated expression of the redundant gene pair MYB33 and MYB65. This prediction was confirmed; the pleiotropic developmental defects of mir159ab are suppressed through the combined mutations of MYB33 and MYB65, demonstrating the narrow and specific target range of miR159a and miR159b.

Background Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL. Methods In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR. Results BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes. Conclusion Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.