Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies with serious impact on patient quality of life due to a reduced rate of response to chemotherapy or radiation therapy. MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that upregulated miR-21 could serve as a potential biomarker for human cancer diagnosis. Considering the target genes identified for miR-21 in HNSCC, this transcript is an important player in several cellular processes that control carcinogenesis. The abnormal expression of miR-21 in this group of pathologies has been assessed in several publications, but given the heterogeneity of the published results, a meta-analysis and proper bioinformatics analysis of expression databases are needed to correctly establish the prognostic potential of this molecule. The present meta-analysis comprises the published survival data on HNSCC patients, reported as HR and 95% CI, in association with the expression levels of miR-21. Our investigation revealed that miR-21 could be used successfully as a prognostic biomarker in HNSCC patients, confirming its oncogenic potential. Specifically, the upregulation of miR-21 in these patients predicts a worse outcome in terms of survival rate.
- Keywords
- bioinformatics analysis, head and neck cancer, miR-21, prognostic, survival,
- Publication type
- Journal Article MeSH
- Review MeSH
MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts' differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.
- Keywords
- differentiation, miR-21-5p, osteoblasts, osteoclasts, osteogenesis, precursor cells,
- MeSH
- Cell Differentiation genetics MeSH
- Cell Line MeSH
- Extracellular Matrix metabolism MeSH
- Coculture Techniques MeSH
- Tartrate-Resistant Acid Phosphatase metabolism MeSH
- RNA, Messenger genetics MeSH
- MicroRNAs genetics metabolism MeSH
- Mice MeSH
- Osteoblasts metabolism MeSH
- Osteogenesis genetics MeSH
- Osteoclasts metabolism MeSH
- Osteopontin genetics metabolism MeSH
- Paracrine Communication genetics MeSH
- Core Binding Factor Alpha 1 Subunit genetics metabolism MeSH
- Bone Resorption metabolism MeSH
- Signal Transduction genetics MeSH
- Transfection MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acp5 protein, mouse MeSH Browser
- Tartrate-Resistant Acid Phosphatase MeSH
- RNA, Messenger MeSH
- MicroRNAs MeSH
- MIRN21 microRNA, mouse MeSH Browser
- Osteopontin MeSH
- Core Binding Factor Alpha 1 Subunit MeSH
- Runx2 protein, mouse MeSH Browser
- Spp1 protein, mouse MeSH Browser
Evidence on equilibrative nucleoside transporter 1 (ENT1) and microRNA-21 (miR‑21) is not yet sufficiently convincing to consider them as prognostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the prognostic value of ENT1/ENT1, miR-21, and neurogenic locus homolog protein 3 gene (NOTCH3) in a well-defined cohort of resected patients treated with adjuvant gemcitabine chemotherapy (n = 69). Using a combination of gene expression quantification in microdissected tissue, immunohistochemistry, and univariate/multivariate statistical analyses we did not confirm association of ENT1/ENT1 and NOTCH3 with improved disease-specific survival (DSS). Low miR-21 was associated with longer DSS in patients with negative regional lymph nodes or primary tumor at stage 1 and 2. In addition, downregulation of ENT1 was observed in PDAC of patients with high ENT1 expression in normal pancreas, whereas NOTCH3 was upregulated in PDAC of patients with low NOTCH3 levels in normal pancreas. Tumor miR‑21 was upregulated irrespective of its expression in normal pancreas. Our data confirmed that patient stratification based on expression of ENT1/ENT1 or miR‑21 is not ready to be implemented into clinical decision-making processes. We also conclude that occurrence of ENT1 and NOTCH3 deregulation in PDAC is dependent on their expression in normal pancreas.
The Aim of this study was to evaluate the expression levels of miR-21, miR-221, miR-150, let-7a and miR-126a in peripheral blood of 71 patients with colorectal cancer and 80 matched healthy control individuals. We determined expression levels of these microRNAs in peripheral blood samples and used small nucleolar RNA (RNU48) as an internal control. Expression levels of miR-21 (p<0.0001) and miR-221 (p<0.0001) were significantly higher, whereas expression levels of miR-150 (p=0.0054) were significantly lower in the blood samples of patients with colorectal cancer in comparison to the control group. The combination of these three microRNAs enabled us to distinguish patients with colorectal cancer from healthy donors with a sensitivity of 80% and specificity of 74% (p<0.0001). We did not observe any correlation of the studied microRNAs with clinicopathological features of colorectal cancer, indicating that expression of these microRNAs is more likely related to the host response to the tumour than the tumour itself.
- Keywords
- Colorectal cancer, biomarker, miRNA expression, microRNAs,
- MeSH
- Colorectal Neoplasms blood genetics MeSH
- Humans MeSH
- MicroRNAs blood MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN150 microRNA, human MeSH Browser
- MIRN21 microRNA, human MeSH Browser
- MIRN221 microRNA, human MeSH Browser
BACKGROUND: Tumors occurring in the sinonasal area are characterized by unfavorable outcome due to difficult diagnosis, treatment, and prognosis of the disease corresponding with the anatomic complexity of the area. METHODS: We used quantitative real-time polymerase chain reaction (PCR) to compare relative expression of miR-21, miR-141, and miR-200c in 70 formalin-fixed, paraffin-embedded samples of sinonasal carcinoma tissue (majority of squamous cell carcinoma [SCC] samples) with 17 control samples of sinonasal tissue. RESULTS: Our data showed significant upregulation of miR-21 in sinonasal cancer tissue. Expression levels of miR-141 and miR-200c were below detectable levels in both sinonasal cancer samples and healthy tissue. Kaplan-Meier analysis with log-rank survival showed that patients with SCC with high expression of miR-21 (highest quartile) had impaired survival close to reaching statistical significance (P = .0630). CONCLUSION: Our results suggest that miR-21 upregulation is involved in tumorigenesis of sinonasal carcinoma and that it is associated with poor prognosis. Thus, miR-21 could be used as a valuable prognostic biomarker.
- Keywords
- biomarker, head and neck cancer, miR-21, microRNA, sinonasal carcinoma,
- MeSH
- Survival Analysis MeSH
- Analysis of Variance MeSH
- Immunohistochemistry MeSH
- Biopsy, Needle MeSH
- Kaplan-Meier Estimate MeSH
- Real-Time Polymerase Chain Reaction methods MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Biomarkers, Tumor genetics MeSH
- Paranasal Sinus Neoplasms genetics mortality pathology surgery MeSH
- Statistics, Nonparametric MeSH
- Prognosis MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- Reproducibility of Results MeSH
- Aged MeSH
- Carcinoma, Squamous Cell genetics mortality pathology surgery MeSH
- Gene Expression Profiling MeSH
- Case-Control Studies MeSH
- Up-Regulation MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN21 microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
OBJECTIVES: Development and metastases of colorectal cancer (CRC) are characterized by multiple genetic alterations. MicroRNAs (miRNAs) are endogenously expressed regulatory noncoding RNAs. Previous, mainly preclinical studies showed altered expression levels of several miRNAs in CRC. METHODS: In our study, the expression levels of miR-21, miR-31, miR-143 and miR-145 in 29 primary colorectal carcinomas and 6 non-tumor adjacent tissue specimens were examined by real-time polymerase chain reaction. miRNA expression levels were also correlated with commonly used clinicopath-ologic features of CRC. RESULTS: Expression levels of analyzed miRNAs significantly differed among tumors and adjacent non-tumor tissues: miR-21 (p = 0.0001) and miR-31 (p = 0.0006) were upregulated, and miR-143 (p = 0.011) and miR-145 (p = 0.003) were downregulated in tumors. For the first time, a high expression of miR-21 was associated with lymph node positivity (p = 0.025) and the development of distant metastases (p = 0.009) in CRC patients. Thus, expression of miR-21 correlated with CRC clinical stage (p = 0.032). Furthermore, tumors >50 mm in maximal tumor diameter were characterized by lower expression of miR-143 (p = 0.006) and miR-145 (p = 0.003). We found no correlation between analyzed miRNAs and serum levels of carcinoembryonic antigen. CONCLUSION: Our results suggest possible roles of miR-21, miR-31, miR-143 and miR-145 in CRC.
- MeSH
- Colorectal Neoplasms genetics physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN21 microRNA, human MeSH Browser
BACKGROUND: Esophageal cancer is the malignant tumor with very poor prognosis and increasing incidence often diagnosed at very late stage, so the prognosis of affected patients is unsatisfactory, despite the development of therapeutic option such as surgery, chemotherapy and radiotherapy. Consequently, there is a great need for biomarkers to allow a tailored multimodality approach with increased efficiency. Altered expression of microRNAs has been reported in wide range of malignancies, including esophageal cancer. The aim of this study was to examine the expression levels of candidate microRNAs in esophageal cancer and evaluate their diagnostic and prognostic potential. FINDINGS: Using quantitative real-time PCR, expression levels of 9 candidate microRNAs were examined in 62 tissue samples, 23 esophageal adenocarcinomas, 22 esophageal squamous cell carcinomas and 17 adjacent esophageal mucosa samples. MicroRNA expression levels were further analyzed in regards to clinico-pathological features of esophageal cancer patients. We observed significantly decreased levels of miR-203 and increased levels of miR-21 in adenocarcinoma tissues when compared to normal mucosa. MiR-29c and miR-148 indicated good ability to distinguish between histological subtypes of esophageal cancer. MiR-203 and miR-148 were linked to disease-free survival and overall survival in esophageal adenocarcinoma patients, and miR-148 also in esophageal squamous cell carcinoma patients. CONCLUSIONS: Our data suggest that altered expression of miR-21, miR-29c, miR-148 and miR-203 are related to neoplastic transformation and progression of the disease and these microRNAs could serve as a potential diagnostic and prognostic biomarkers in esophageal cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4646922201567057.
- MeSH
- Adenocarcinoma diagnosis genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Biomarkers, Tumor analysis genetics metabolism MeSH
- Esophageal Neoplasms diagnosis genetics MeSH
- Prognosis MeSH
- Gene Expression Regulation, Neoplastic genetics MeSH
- Aged MeSH
- Esophageal Squamous Cell Carcinoma MeSH
- Carcinoma, Squamous Cell diagnosis genetics MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN148 microRNA, human MeSH Browser
- MIRN203 microRNA, human MeSH Browser
- MIRN21 microRNA, human MeSH Browser
- MIRN29a microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
MicroRNAs, which are endogenously expressed regulatory noncoding RNAs, have an altered expression in colorectal cancer. The aim of our study was to assess the relationship of miR-21 and miR-143 expression to the prognostic/clinicopathological features of colorectal carcinoma (CRC) and colorectal liver metastases (CLM). The estimation was performed in 46 paired (tumor and control) tissue samples of CRC. Further, we studied 30 tissue samples of CLM. MiR-21 and miR-143 expressions were quantified by using the quantitative reverse transcription polymerase chain reaction method. Relation of miR-21 and miR-143 expression to disease-free interval (DFI) (Wilcoxon; P = 0.0026 and P = 0.0191, respectively) was recorded. There was shorter DFI in patients with a higher expression of miR-21 and, surprisingly, also in patients with a higher expression of miR-143, which is a putative tumor suppressor. There was a higher expression of miR-21 and lower expression of miR-143 in CRC tissue in comparison with adjacent normal colon tissue (P < 0.0001; P < 0.0001, respectively). Similarly, we observed a higher expression of miR-21 and a lower expression of miR-143 in CLM in comparison with normal colon tissue (P < 0.0001; P < 0.0001, respectively). Our results support the hypothesis about oncogenic function of miR-21 and show its relation to DFI. The role of miR-143 in carcinogenesis seems to be more complex.
- MeSH
- Adult MeSH
- Colorectal Neoplasms genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs analysis physiology MeSH
- Liver Neoplasms secondary MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN143 microRNA, human MeSH Browser
- MIRN21 microRNA, human MeSH Browser
Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor; patients with GBM often have a very poor prognosis and differing responses to treatment. Therefore, it is very important to find new biomarkers that can predict clinical outcomes and help in treatment decisions. MicroRNAs are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and play a key role in the pathogenesis of GBM. In a group of 38 patients with primary GBM, we analyzed the expression of eight microRNAs (miR-21, miR-128a, miR-181c, miR-195, miR-196a, miR-196b, miR-221, and miR-222). In addition, we examined the methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter by high-resolution melting analysis, as this has been shown to be a predictive marker in GBM. MGMT methylation status correlated with progression-free survival (P = 0.0201; log-rank test) as well as with overall survival (P = 0.0054; log-rank test). MiR-195 (P = 0.0124; log-rank test) and miR-196b (P = 0.0492; log-rank test) positively correlated with overall survival. Evaluation of miR-181c in combination with miR-21 predicted time to progression within 6 months of diagnosis with 92% sensitivity and 81% specificity (P < 0.0001). Our data confirmed that the methylation status of MGMT but also miR-21, miR-181c, miR-195, and miR-196b to be associated with survival of GBM patients. Above all, we suggest that the combination of miR-181c and miR-21 could be a very sensitive and specific test to identify patients at high risk of early progression after surgery.
- MeSH
- DNA Modification Methylases genetics metabolism MeSH
- Adult MeSH
- DNA Repair Enzymes genetics metabolism MeSH
- Glioblastoma diagnosis genetics metabolism mortality MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- DNA Methylation MeSH
- MicroRNAs biosynthesis MeSH
- Biomarkers, Tumor genetics metabolism MeSH
- Tumor Suppressor Proteins genetics metabolism MeSH
- Brain Neoplasms diagnosis genetics metabolism mortality MeSH
- Disease-Free Survival MeSH
- Prognosis MeSH
- Promoter Regions, Genetic * MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Modification Methylases MeSH
- DNA Repair Enzymes MeSH
- MGMT protein, human MeSH Browser
- MicroRNAs MeSH
- MIrn181 microRNA, human MeSH Browser
- MIRN195 microRNA, human MeSH Browser
- MIRN196 microRNA, human MeSH Browser
- MIRN21 microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
- Tumor Suppressor Proteins MeSH
Blood plasma microRNAs (miRNAs) are emerging as a clinically useful tool for non-invasive detection and prognosis estimation in various cancer types including pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to provide an independent validation of circulating miRNAs identified in previous studies as diagnostic and/or prognostic biomarkers in PDAC. Based on the literature search, 6 miRNAs were chosen as candidates for independent validation; miR-21-5p, miR-375, miR-155, miR-17-5p, miR-126-5p and miR-1290. Validation of these miRNAs was performed in a cohort of 25 patients with PDAC undergoing surgical resection and 24 healthy donors. Plasma levels of miRNAs were determined using quantitative real-time PCR. We confirmed significantly higher levels of all tested miRNA in blood plasma of PDAC patients in comparison to healthy controls with miR-21-5p showing the highest analytical performance (p<0.001; AUC>0.99). Increased levels of miR-21-5p (p=0.045) and miR-375 (p=0.013) were significantly associated with overall survival. Multivariate analysis demonstrated that miR-21-5p is a significant unfavorable prognostic factor independent on other clinical variables including adjuvant chemotherapy (hazard ratio 2.95; 95% CI 1.06-8.18; p=0.038). Our preliminary data indicate promising diagnostic and prognostic utility of plasma miR-21-5p in PDAC patients.
- Keywords
- Pancreatic ductal adenocarcinoma, diagnosis, miR-21-5p, microRNAs, plasma, prognosis,
- MeSH
- Adenocarcinoma blood pathology surgery MeSH
- Carcinoma, Pancreatic Ductal blood pathology surgery MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs blood MeSH
- Survival Rate MeSH
- Biomarkers, Tumor metabolism MeSH
- Pancreatic Neoplasms blood pathology surgery MeSH
- Follow-Up Studies MeSH
- Preoperative Care * MeSH
- Prognosis MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN21 microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
