MicroRNAs (miRNAs) have emerged as important regulators of gene expression in various biological processes, including cancer. miR-182-5p has gained attention for its potential implications in gynecologic cancers, including breast, ovarian, endometrial, and cervical cancers. miR-182-5p dysregulation has been associated with multiple facets of tumor biology in gynecologic cancers, including tumor initiation, progression, metastasis, and therapeutic response. Studies have highlighted its involvement in key signaling pathways and cellular processes that contribute to cancer development and progression. In addition, miR-182-5p has shown potential as a diagnostic and prognostic biomarker, with studies demonstrating its correlation with clinicopathological features and patient outcomes. Furthermore, the therapeutic potential of miR-182-5p is being explored in gynecologic cancers. Strategies such as miRNA mimics or inhibitors targeting miR-182-5p have shown promise in preclinical and early clinical studies. These approaches aim to modulate miR-182-5p expression, restoring normal cellular functions and potentially enhancing treatment responses. Understanding the biologic and clinical implications of miR-182-5p in gynecologic cancers is crucial for the development of targeted therapeutic strategies and personalized medicine approaches. Further investigations are needed to unravel the specific target genes and pathways regulated by miR-182-5p. It is important to consider the emerging biologic and clinical implications of miR-182-5p in gynecologic cancers.
PURPOSE: TACE induces variable systemic effects by producing factors that promote inflammation, oncogenesis, and angiogenesis. Here we compare concentrations of microRNAs (miR-21, miR-210 and miR-34a) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) patients undergoing TACE with degradable (DSM) and nondegradable (DEB) particles and potential use of these biomarker changes for prediction of patient outcomes. MATERIALS AND METHODS: Overall, 52 patients with HCC treated with DSM TACE (24 patients) and DEB TACE (28 patients) were included in this prospective study. Concentrations of studied biomarkers were measured from blood plasma preprocedurally, immediately (< 90 min) postprocedurally, and 24-h after TACE. Levels were compared between DSM and DEB TACE and correlated with treatment response six and 12 months after the first TACE. RESULTS: Both DSM and DEB TACE elevated plasma levels of miR-21, miR-34a, and miR-210 at 24 h post-procedure compared to baseline levels (FC 1.25-4.0). MiR-34a elevation immediately after TACE was significantly associated with nonprogressive disease compared to those with progressive disease at both six months (FCa: p = 0.014) and 12 months (FCa: p = 0.029) post-TACE. No significant biomarker changes were found between the embolization particle groups. However, VEGF levels showed a decrease only in the DSM TACE group (FC24: p = < 0.001). CONCLUSION: Embolization particle type did not significantly impact miRNA or VEGF changes post-TACE. However, miR-34a elevation immediately after the procedure predicts better patient outcome and may prove useful as a biomarkers for the monitoring of clinical outcomes. LEVEL OF EVIDENCE: Level 3 Prospective cohort study.
- MeSH
- biologické markery krev MeSH
- chemoembolizace * metody MeSH
- hepatocelulární karcinom * terapie krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- nádorové biomarkery * krev MeSH
- nádory jater * terapie genetika krev MeSH
- prospektivní studie MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor A * krev MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155-5p (miR-155, MIR155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research. METHODS: We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the MIR155HG gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation. RESULTS: The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 (CCND1). We confirmed the overexpression of canonical miR-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets (FCRL5, ISG15, and MX1). CONCLUSIONS: We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the MIR155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.
- MeSH
- chronická lymfatická leukemie * genetika patologie MeSH
- cyklin D1 genetika metabolismus MeSH
- inhibitor p21 cyklin-dependentní kinasy * genetika metabolismus MeSH
- kontrolní body buněčného cyklu * genetika MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- proliferace buněk genetika MeSH
- proteiny teplotního šoku MeSH
- regulace genové exprese u leukemie MeSH
- transportní proteiny genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Acute kidney injury (AKI) due to gentamicin nephrotoxicity is a significant concern in clinical medicine, particularly in patients receiving prolonged or high-dose gentamicin therapy. Gentamicin is an aminoglycoside antibiotic frequently used in the treatment of a range of bacterial infections. However, its use is associated with nephrotoxicity which can manifest as AKI. Due to this, it is crucial to diagnose promptly and manage treatment effectively. Ongoing studies are therefore focusing on non-protein-coding RNAs as potential biomarkers for AKI. Numerous microRNAs (miRNAs) have been implicated in gentamicin-induced nephrotoxicity and AKI. They participate in pathways associated with inflammation, cell death, and oxidative stress and each of these factors play critical roles in the development of gentamicin-induced kidney injury. Research studies have demonstrated changes in the expression levels of these miRNAs in response to gentamicin exposure both in vitro and in in vivo models, as well as in human clinical trials involving patients receiving gentamicin therapy. The dysregulation of these miRNAs correlates with the severity of kidney injury and may serve as sensitive biomarkers for early detection and monitoring of AKI induced by gentamicin.
INTRODUCTION: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers. METHODS: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data. RESULTS: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations. CONCLUSION: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice. INTRODUCTION: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers. METHODS: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data. RESULTS: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations. CONCLUSION: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice.
- MeSH
- dospělí MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové biomarkery * genetika metabolismus MeSH
- nádory prsu * patologie genetika metabolismus mortalita MeSH
- regulace genové exprese u nádorů * MeSH
- RNA malá jaderná * genetika metabolismus MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) is a rare but serious condition requiring accurate diagnostics. Cerebrospinal fluid (CSF) analysis plays a crucial role, particularly in cases where biopsy is not feasible, and imaging is inconclusive. AREAS COVERED: Chemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including circulating tumor DNA (ctDNA) analysis and microRNAs (miRNAs), are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data.This review examines both traditional and emerging methods for CSF analysis in diagnosing CNS involvement in DLBCL. Conventional approaches such as cytomorphology, flow cytometry, and biochemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including ctDNA analysis and miRNAs, are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data. EXPERT OPINION: Advancements in CSF biomarker analysis are improving the diagnosis of CNS lymphoma, aiding early detection and personalized treatment approaches. However, further research and broader clinical validation are necessary for their routine implementation.
- MeSH
- cirkulující nádorová DNA mozkomíšní mok genetika MeSH
- diagnostické techniky molekulární metody MeSH
- difúzní velkobuněčný B-lymfom * diagnóza mozkomíšní mok genetika patologie MeSH
- interleukin-10 genetika mozkomíšní mok MeSH
- lidé MeSH
- meningeální nádory * diagnóza mozkomíšní mok genetika MeSH
- mikro RNA genetika mozkomíšní mok MeSH
- mutace MeSH
- myeloidní diferenciační faktor 88 genetika MeSH
- nádorové biomarkery * mozkomíšní mok genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Dysregulation of extracellular matrix (ECM) homeostasis plays a pivotal role in the accelerated degradation of cartilage, presenting a notable challenge for effective osteoarthritis (OA) treatment and cartilage regeneration. In this study, we introduced an injectable hydrogel based on streamlined-zinc oxide (ZnO), which is responsive to matrix metallopeptidase (MMP), for the delivery of miR-17-5p. This approach aimed to address cartilage damage by regulating ECM homeostasis. The ZnO/miR-17-5p composite functions by releasing zinc ions to attract native bone marrow mesenchymal stem cells, thereby fostering ECM synthesis through the proliferation of new chondrocytes. Concurrently, sustained delivery of miR-17-5p targets enzymes responsible for matrix degradation, thereby mitigating the catabolic process. Notably, the unique structure of the streamlined ZnO nanoparticles is distinct from their conventional spherical counterparts, which not only optimizes the rheological and mechanical properties of the hydrogels, but also enhances the efficiency of miR-17-5p transfection. Our male rat model demonstrated that the combination of streamlined ZnO, MMP-responsive hydrogels, and miRNA-based therapy effectively managed the equilibrium between catabolism and anabolism within the ECM, presenting a fresh perspective in the realm of OA treatment.
- MeSH
- buněčná diferenciace * účinky léků MeSH
- chondrocyty metabolismus účinky léků cytologie MeSH
- chrupavka * účinky léků MeSH
- extracelulární matrix * metabolismus účinky léků MeSH
- homeostáza účinky léků MeSH
- hydrogely * chemie MeSH
- kloubní chrupavka účinky léků MeSH
- krysa rodu rattus MeSH
- matrixové metaloproteinasy metabolismus MeSH
- mezenchymální kmenové buňky cytologie účinky léků metabolismus MeSH
- mikro RNA genetika metabolismus MeSH
- osteoartróza terapie patologie MeSH
- oxid zinečnatý chemie MeSH
- potkani Sprague-Dawley MeSH
- regenerace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The poor prognosis of colorectal cancer (CRC) contributes to a yearly increase in CRC mortality, while microRNAs (miRNAs) were found to play a regulatory function in diversiform cancers, including CRC. The objective of this research was to evaluate the clinical value and possible regulatory mechanisms of miR-767-5p in CRC. The expression level of miR-767-5p in CRC tissues and cells was examined. The Kaplan-Meier curve was utilized to analyse the function of miR-767-5p in CRC prognosis. The independent prognostic factors in CRC were assessed by a multivariate COX regression analysis. Additionally, the regulatory mechanism of miR-767-5p in CRC was determined through an in vitro cell experiment. The miR-767-5p expression was down-regulated in CRC tumour tissues and CRC cells. Indicators such as tumour differentiation, TNM, LNM and miR-767-5p were identified as independent prognostic factors for a poor CRC prognosis. The regulatory relationship between miR-767-5p and nuclear factor I A (NFIA) was verified by the dual-luciferase reporter assay, and the NFIA expression level was significantly suppressed by over-expressed miR-767-5p. The proliferation, migration and invasion of CRC cells were inhibited by over-expressing miR-767-5p, while the inhibition effect could be reversed by over-expressing NFIA. The over-expressed miR-767-5p could serve as a tumour suppressor to inhibit the progression of CRC by suppressing the expression level of NFIA.
- MeSH
- invazivní růst nádoru MeSH
- Kaplanův-Meierův odhad MeSH
- kolorektální nádory * genetika patologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- pohyb buněk genetika MeSH
- prognóza MeSH
- proliferace buněk genetika MeSH
- regulace genové exprese u nádorů * MeSH
- senioři MeSH
- transkripční faktory NFI metabolismus genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Nucleus pulposus cells (NPC) are important for the development of intervertebral disc degeneration (IVDD). miR-4478 can aggravate IVDD, but whether it can aggravate IVDD by regulating ferroptosis in NPC remains unclear. The optimal level of ferroptosis activator RSL3 for eliciting ferroptosis in NPC was screened by Western blot and CCK-8 assay. The targeting relationship between miR-4478 and its potential target solute carrier family 7 member 11 (SLC7A11) was explored based on dual luciferase assay. On this basis, IVDD models were constructed. After over-expression or knockdown of miR-4478 or SLC7A11, CCK-8 and calcein-AM/PI assays were employed to evaluate cell damage. Flow cytometry, Western blot and Prussian blue staining were employed to evaluate oxidation and ferroptosis levels, and histopathological staining was applied to evaluate the intervertebral disc tissue injury degree. The optimal concentration of RSL3 was 1 μM. Under these conditions, miR-4478 or SLC7A11 can be effectively over-expressed or knocked down after transfection. Knockdown of miR-4478 can improve the survival rate of NPC, the level of Fe2+ ions, improve the pathological damage of intervertebral disc structure, reduce iron deposition in tissues, and significantly reduce expression of reactive oxygen species (ROS) and ferroptosis-related protein. The levels of antioxidant enzymes were significantly increased. When miR-4478 was over-expressed, the above phenomenon was reversed. On this basis, after SLC7A11 was over-expressed, the effect of miR-4478 up-regulation was weakened, and NPC ferroptosis was improved. miR-4478 can target SLC7A11 to promote NPC damage, peroxide accumulation and iron metabolism disorders, leading to ferroptosis, thereby inducing IVDD.
- MeSH
- degenerace meziobratlové ploténky * metabolismus genetika patologie MeSH
- ferroptóza * genetika MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mikro RNA * metabolismus genetika MeSH
- nucleus pulposus * metabolismus patologie cytologie MeSH
- potkani Sprague-Dawley MeSH
- transportní systém aminokyselin y+ * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The selection of proper reference genes and materials is critical in the design of PCR experiments, especially for differential expression studies. In this study, we propose a method to identify robust endogenous control miRNAs in the visceral adipose tissue of C57BL/6J mice with non-alcoholic fatty liver disease induced by alternating Western and control diets. This study outlines a comprehensive methodology for the analysis of microRNA endogenous controls using microfluidic cards in conjunction with miRNA profiling through small RNA sequencing and subsequent validation by quantitative PCR and the RefFinder algorithm. Criteria included were fold change, p-value, reads per million, and gene stability assessment. A set of six putative endogenous microRNAs was identified (miR-331-3p, let-7a-5p, miR-1839-5p, miR-151a-5p, let-7d-5p, and let-7c-5p). Subsequent validation and analysis using the RefFinder algorithm assessed the stability of the selected genes, and a combination of the three most stable endogenous miRNA controls (miR-331-3p, let-7a- 5p, and miR-1839-5p) exhibiting consistent expression patterns with minimal variability was set. Given the absence of universal endogenous controls, individual evaluation of normalizers for each experiment is imperative for accurate miRNA expression measurements. This approach, which combines multiple techniques and assessments, provides a reliable strategy for identifying and validating endogenous controls in miRNA studies.
- MeSH
- algoritmy MeSH
- mikro RNA * genetika metabolismus MeSH
- modely nemocí na zvířatech * MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nealkoholová steatóza jater * genetika metabolismus patologie MeSH
- nitrobřišní tuk * metabolismus MeSH
- regulace genové exprese MeSH
- stanovení celkové genové exprese metody MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
