scholarly journals miRNA Clusters with Up-Regulated Expression in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2979
Author(s):  
Paulína Pidíková ◽  
Iveta Herichová
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Expression Patterns ◽  
Clinicopathological Characteristics ◽  
Cancer Tissue ◽  
Poor Patient ◽  
Regulated Expression ◽  
Mirna Clusters ◽  
Non Coding Rnas ◽  
Poor Patient Survival

Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their members with respect to clinicopathological characteristics of patients. Based on available data, 15 up-regulated clusters, miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224, were selected. The positions of such clusters in the genome can be intronic or intergenic. Most clusters are regulated by several transcription factors, and miRNAs are also sponged by specific long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. Based on experimental evidence, 181 target genes of selected clusters were identified. Panther analysis was used to reveal the functions of the target genes and their corresponding pathways. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research.

scholarly journals miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation

2020 ◽  
Vol 21 (13) ◽  
pp. 4633 ◽  
Author(s):  
Paulína Pidíkova ◽  
Richard Reis ◽  
Iveta Herichova
Keyword(s):  
Colorectal Cancer ◽  
Transcriptional Control ◽  
In Vitro Models ◽  
Mirna Regulation ◽  
Regulated Expression ◽  
Mirna Clusters ◽  
Position Regulation ◽  
Non Coding Rnas

Regulation of microRNA (miRNA) expression has been extensively studied with respect to colorectal cancer (CRC), since CRC is one of the leading causes of cancer mortality worldwide. Transcriptional control of miRNAs creating clusters can be, to some extent, estimated from cluster position on a chromosome. Levels of miRNAs are also controlled by miRNAs “sponging” by long non-coding RNAs (ncRNAs). Both types of miRNA regulation strongly influence their function. We focused on clusters of miRNAs found to be down-regulated in CRC, containing miR-1, let-7, miR-15, miR-16, miR-99, miR-100, miR-125, miR-133, miR-143, miR-145, miR-192, miR-194, miR-195, miR-206, miR-215, miR-302, miR-367 and miR-497 and analysed their genome position, regulation and functions. Only evidence provided with the use of CRC in vivo and/or in vitro models was taken into consideration. Comprehensive research revealed that down-regulated miRNA clusters in CRC are mostly located in a gene intron and, in a majority of cases, miRNA clusters possess cluster-specific transcriptional regulation. For all selected clusters, regulation mediated by long ncRNA was experimentally demonstrated in CRC, at least in one cluster member. Oncostatic functions were predominantly linked with the reviewed miRNAs, and their high expression was usually associated with better survival. These findings implicate the potential of down-regulated clusters in CRC to become promising multi-targets for therapeutic manipulation.

MicroRNAs and their role in hematological malignant diseases

2012 ◽  
Vol 153 (52) ◽  
pp. 2051-2059 ◽  
Author(s):  
Zsuzsanna Gaál ◽  
Éva Oláh
Keyword(s):  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Cancer Tissue ◽  
Altered Expression ◽  
Diagnosis And Prognosis ◽  
Oncologic Patients ◽  
Different Types ◽  
Non Coding Rnas ◽  
Success Of Treatment ◽  
Posttranscriptional Level

MicroRNAs are a class of small non-coding RNAs regulating gene expression at posttranscriptional level. Their target genes include numerous regulators of cell cycle, cell proliferation as well as apoptosis. Therefore, they are implicated in the initiation and progression of cancer, tissue invasion and metastasis formation as well. MicroRNA profiles supply much information about both the origin and the differentiation state of tumours. MicroRNAs also have a key role during haemopoiesis. An altered expression level of those have often been observed in different types of leukemia. There are successful attempts to apply microRNAs in the diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia. Measurement of the expression levels may help to predict the success of treatment with different kinds of chemotherapeutic drugs. MicroRNAs are also regarded as promising therapeutic targets, and can contribute to a more personalized therapeutic approach in haemato-oncologic patients. Orv. Hetil., 2012, 153, 2051–2059.

scholarly journals Emerging microRNA biomarkers for colorectal cancer diagnosis and prognosis

Open Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 180212 ◽  
Author(s):  
Bing Chen ◽  
Zijing Xia ◽  
Ya-Nan Deng ◽  
Yanfang Yang ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Research Use ◽  
Biological Processes ◽  
Functional Roles ◽  
Analytical Technique ◽  
Diagnosis And Prognosis ◽  
Recurrence Prediction ◽  
Extracellular Mirnas ◽  
Non Coding Rnas

MicroRNAs (miRNAs) are one abundant class of small, endogenous non-coding RNAs, which regulate various biological processes by inhibiting expression of target genes. miRNAs have important functional roles in carcinogenesis and development of colorectal cancer (CRC), and emerging evidence has indicated the feasibility of miRNAs as robust cancer biomarkers. This review summarizes the progress in miRNA-related research, including study of its oncogene or tumour-suppressor roles and the advantages of miRNA biomarkers for CRC diagnosis, treatment and recurrence prediction. Along with analytical technique improvements in miRNA research, use of the emerging extracellular miRNAs is feasible for CRC diagnosis and prognosis.

scholarly journals Global Profiling of lncRNAs Expression Responsive to Allopolyploidization in Cucumis

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1500
Author(s):  
Panqiao Wang ◽  
Xiaqing Yu ◽  
Zaobing Zhu ◽  
Yufei Zhai ◽  
Qinzheng Zhao ◽  
...  
Keyword(s):  
Target Genes ◽  
Genome Duplication ◽  
Chlorophyll Synthesis ◽  
Plant Evolution ◽  
Biological Regulation ◽  
F1 Hybrid ◽  
Regulated Expression ◽  
Intergenic Regions ◽  
Non Coding Rnas ◽  
Insight Into

Long non-coding RNAs (lncRNAs) play critical regulatory roles in various biological processes. However, the presence of lncRNAs and how they function in plant polyploidy are still largely unknown. Hence, we examined the profile of lncRNAs in a nascent allotetraploid Cucumis hytivus (S14), its diploid parents, and the F1 hybrid, to reveal the function of lncRNAs in plant-interspecific hybridization and whole genome duplication. Results showed that 2206 lncRNAs evenly transcribed from all 19 chromosomes were identified in C. hytivus, 44.6% of which were from intergenic regions. Based on the expression trend in allopolyploidization, we found that a high proportion of lncRNAs (94.6%) showed up-regulated expression to varying degrees following hybridization. However, few lncRNAs (33, 2.1%) were non-additively expressed after genome duplication, suggesting the significant effect of hybridization on lncRNAs, rather than genome duplication. Furthermore, 253 cis-regulated target genes were predicted for these differentially expressed lncRNAs in S14, which mainly participated in chloroplast biological regulation (e.g., chlorophyll synthesis and light harvesting system). Overall, this study provides new insight into the function of lncRNAs during the processes of hybridization and polyploidization in plant evolution.

scholarly journals High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Athanasios Tampakis ◽  
Ekaterini-Christina Tampaki ◽  
Afrodite Nonni ◽  
Ioannis D. Kostakis ◽  
Alberto Posabella ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Survival Data ◽  
Early Stage ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Disease Recurrence ◽  
Clinicopathological Characteristics ◽  
Early Stage Disease ◽  
Cell Protrusion

Abstract Background Fascin is the main actin cross-linker protein that regulates adhesion dynamics and stabilizes cell protrusion, such as filopodia. In human cancer, fascin expression correlates with aggressive clinical features. This study aimed to determine the expression patterns of fascin-1 and assessed its prognostic significance in colorectal cancer. Methods One hundred eleven specimens of patients with primary resectable colorectal cancer were examined via immunohistochemistry for the expression of fascin-1, and the results were correlated with clinicopathological characteristics and survival data. Results Fascin-1 staining displayed strong intensity in the cytoplasm of the colorectal cancer cells and endothelial cells of tumor blood vessels. Moderate to high fascin-1 expression was associated with progressive anatomic disease extent (p < 0.001), higher T classification (p = 0.007), the presence of lymph node (p < 0.001) and distant metastasis (p = 0.002), high grade tumors (p = 0.002) and vascular invasion (p < 0.001). Patients displaying moderate and high fascin-1 expression demonstrated a significantly worse 5-year overall survival [HR; 3.906, (95%CI) = 1.250–12.195] and significantly worse 3-year progression-free survival [HR; 3.448, (95%CI) = 1.401–8.475] independent of other clinicopathological characteristics. Besides, high fascin-1 expression in early-stage cancer only was associated with a dismal prognosis. Conclusions High fascin-1 expression in colorectal cancer is an independent negative prognostic factor for survival, increasing the risk for disease recurrence or death almost by sevenfold. Fascin-1 expression could be potentially utilized to identify high-risk patients prone to metastasis already in early-stage disease.

scholarly journals The extracellular sulfatase SULF2 promotes liver tumorigenesis by stimulating assembly of a promoter-looping GLI1-STAT3 transcriptional complex

2020 ◽  
Vol 295 (9) ◽  
pp. 2698-2712 ◽  
Author(s):  
Ryan M. Carr ◽  
Paola A. Romecin Duran ◽  
Ezequiel J. Tolosa ◽  
Chenchao Ma ◽  
Abdul M. Oseini ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Cytokine Signaling ◽  
Specific Gene ◽  
Suppressor Of Cytokine Signaling ◽  
Poor Patient ◽  
Human Orthologs ◽  
Transcriptional Complex ◽  
Transcription 3 ◽  
Poor Patient Survival

The expression of the extracellular sulfatase SULF2 has been associated with increased hepatocellular carcinoma (HCC) growth and poor patient survival. However, the molecular mechanisms underlying SULF2-associated tumor growth remain unclear. To address this gap, here we developed a transgenic mouse overexpressing Sulf2 in hepatocytes under the control of the transthyretin promoter. In this model, Sulf2 overexpression potentiated diethylnitrosamine-induced HCC. Further analysis indicated that the transcription factor GLI family zinc finger 1 (GLI1) mediates Sulf2 expression during HCC development. A cross of the Sulf2-overexpressing with Gli1-knockout mice revealed that Gli1 inactivation impairs SULF2-induced HCC. Transcriptomic analysis revealed that Sulf2 overexpression is associated with signal transducer and activator of transcription 3 (STAT3)-specific gene signatures. Interestingly, the Gli1 knockout abrogated SULF2-mediated induction of several STAT3 target genes, including suppressor of cytokine signaling 2/3 (Socs2/3); Pim-1 proto-oncogene, Ser/Thr kinase (Pim1); and Fms-related tyrosine kinase 4 (Flt4). Human orthologs were similarly regulated by SULF2, dependent on intact GLI1 and STAT3 functions in HCC cells. SULF2 overexpression promoted a GLI1-STAT3 interaction and increased GLI1 and STAT3 enrichment at the promoters of their target genes. Interestingly, the SULF2 overexpression resulted in GLI1 enrichment at select STAT3 consensus sites, and vice versa. siRNA-mediated STAT3 or GLI1 knockdown reduced promoter binding of GLI1 and STAT3, respectively. Finally, chromatin-capture PCR confirmed long-range co-regulation of SOCS2 and FLT3 through changes in promoter conformation. These findings define a mechanism whereby SULF2 drives HCC by stimulating formation of a GLI1-STAT3 transcriptional complex.

scholarly journals Fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality.

2020 ◽  
Author(s):  
Athanasios Tampakis ◽  
Ekaterini Christina Tampaki ◽  
Afrodite Nonni ◽  
Ioannis D. Kostakis ◽  
Alberto Posabella ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Survival Data ◽  
Early Stage ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Disease Recurrence ◽  
Clinicopathological Characteristics ◽  
Early Stage Disease ◽  
Cell Protrusion

Abstract Background; Fascin is the main actin cross-linker protein that regulates adhesion dynamics and stabilizes cell protrusion, such as filopodia. In human cancer, fascin expression correlates with aggressive clinical features. This study aimed to determine the expression patterns of fascin-1 and assess its prognostic significance in colorectal cancer. Methods; One hundred eleven specimens of patients with primary resectable colorectal cancer were examined via immunohistochemistry for the expression of fascin-1, and the results were correlated with clinicopathological characteristics and survival data. Results; Fascin-1 staining displayed strong intensity in the cytoplasm of the colorectal cancer cells and endothelial cells of tumor blood vessels. Moderate and high fascin-1 expression was associated with progressive anatomic disease extent (p < 0.001), higher T classification (p = 0.007), the presence of lymph node (p < 0.001) and distant metastasis (p = 0.002), high grade tumors (p = 0.002) and vascular invasion (p < 0.001). Patients displaying moderate and high fascin-1 expression demonstrated a significantly worse 5-year overall survival [HR; 3.906, (95%CI) = 1.250-12.195] and significantly worse 3-year progression-free survival [HR; 3.448, (95%CI) = 1.401–8.475] independent of other clinicopathological characteristics. Besides, high fascin-1 expression in early-stage cancer only was associated with a dismal prognosis. Conclusions; High fascin-1 expression in colorectal cancer is an independent negative prognostic factor for survival, increasing the risk for disease recurrence or death almost by sevenfold. Fascin-1 expression could be potentially utilized to identify high-risk patients prone to metastasis already in early-stage disease.

scholarly journals Expression of miR-21 in Colorectal Cancer and Its Relationship with Clinicopathological Characteristics of Colorectal Cancer

2020 ◽  
Vol 3 (3) ◽  
pp. 40
Author(s):  
Jia Lei
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Clinicopathological Characteristics ◽  
Control Group ◽  
Cancer Tissue ◽  
Study Group ◽  
Node Metastasis ◽  
The Difference ◽  
Tissue Specimens

Objective: To investigate the expression of miR-21 in colorectal cancer cells, and to analyze the relationship between the level of miR-21 and the clinicopathological characteristics of colorectal cancer patients. Methods: 210 patients with colorectal cancer treated in our hospital from January 2016 to June 2019 were selected. Cancer tissue specimens (study group) and adjacent normal tissue specimens (control group) were surgically collected, and the quantitative quantitative PCR was used to detect and compare the miR-21 expression of the two groups. Results: The expression of miR-21 in the study group was higher than that in the control group, and the difference was statistically significant (P <0.05). There were significant differences among patients with early and intermediate TNM, patients with low differentiation and patients with moderate to high differentiation, patients with lymph node metastasis and patients without lymph node metastasis, patients with high infiltration and patients with low infiltration, patients with high CEA levels, and patients with low CEA, and the difference was statistically significant (P <0.05). Conclusion: In colorectal cancer, miR-21 is highly expressed, which is closely related to stage and differentiation, and can be used to reflect the patient’s condition.

scholarly journals MicroRNA-202 Induces Myoblast to Myocyte Differentiation through Targeting Rock-1

2021 ◽  
Author(s):  
Maryam Honardoost ◽  
Mahsa Bourbour ◽  
Ehsan Arefian
Keyword(s):  
Target Genes ◽  
Horse Serum ◽  
Expression Patterns ◽  
C2c12 Cell ◽  
Inhibitory Effect ◽  
Luciferase Assay ◽  
Differentiation Process ◽  
Myocyte Differentiation ◽  
Non Coding Rnas ◽  
The Impact

Abstract The expression patterns of microRNAs (small non-coding RNAs) are altered in many biological processes such as myogenesis. In this study, we aimed to investigate the impact of predicted miR-202, its target genes Akt2 and Rock-1 as a potential regulator of myoblast in the myocyte differentiation process using the C2C12 cell line. After confirmation of the differentiation process induced by 3% horse serum, the expression level of miRNA and its targets were evaluated. In the following, a luciferase assay was conducted to approve the effect of miRNA on its target. Our results indicated that miR-202 and Akt2 were significantly up-regulated during differentiation, while Rock-1 was downregulated. Co-transfection of miRNA with psiCHECK2-Rock-1 significantly presented that Rock-1 was directly targeted by miR-202. On the contrary, miR-202 has failed to enforce its inhibitory effect on Akt2 expression. In particular, miR-202 seems to be a regulator of muscle differentiation pathway thought targeting Rock-1.

Analysis of Overexpressed miRNA in Circulation and Cancer Tissue to Develop a Potential microRNA Panel for the Diagnosis of Colorectal Cancer

MicroRNA ◽  
2021 ◽  
Vol 11 ◽  
Author(s):  
Babita Pruseth ◽  
Amit Ghosh ◽  
Dibyabhaba Pradhan ◽  
Suvendu Purkait ◽  
Praveen Kumar Guttula
Keyword(s):  
Colorectal Cancer ◽  
Metal Ion ◽  
Target Genes ◽  
Target Identification ◽  
Gene Expression Omnibus ◽  
Vital Role ◽  
Cancer Tissue ◽  
Success Rates ◽  
Metal Ion Binding ◽  
Serum Samples

Background: Colorectal cancer (CRC) represents the world’s fourth deadly cancer, but its early diagnosis can be curative with considerable success rates. This study was aimed to identify CRC specific microRNAs (miRNAs) in tissue and serum samples to develop a miRNA-based diagnostics panel for the minimal invasive detection of CRC in early condition. Methods: By integrating four microarrays in tissue and serum samples of CRC from Gene Expression Omnibus (GEO) database, we screened out the highly expressed miRNAs in each dataset by using limma R package. Two important upregulated miRNAs namely hsa-miR-1246 and hsa-miR-1825 were overlapped in both tissue and serum samples of CRC, and were investigated to target identification, followed by functional annotation and protein- protein interaction (PPI) study for the target genes through DAVID and STRING respectively. Finally, hub target genes were retrieved by Cytoscape analysis. Results: It was shown that target genes of hsa-miR-1246 and hsa-miR-1825 were involved with core KEGG pathways (such as cAMP, PI3K-Akt and calcium signaling pathway). In addition, biological processes (such as cell adhesion and cell proliferation), cellular components (such as plasma membrane and cytosol), molecular functions (such as protein binding and metal ion binding), were mostly associated with the target genes. Their top 5 target genes were retrieved and their biological function towards tumor progression was shown using Cancer Hallmarks Analytics Tool. Conclusion: This study suggested that hsa-miR-1246 and hsa-miR-1825, as overlapped upregulated tissue and circulating miRNAs might have a vital role in the development of CRC and their five hub target genes were identified.

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