ABSTRACT
We studied the profile of miRNA secreted into culture medium by DU145 prostate cancer cells and identified a subset of miRNAs characterized by the absence of correlation of their content in the cell and medium, which is likely a result of specific secretion. Three of these miRNA, hsa-miR-4417, hsa-miR-3175, and hsa-miR-6782-5p, exhibit the highest expression and are candidate circulating biomarkers for metastatic activity of prostate cancer. Two of these miRNA are coded by introns of genes linked with genome stability maintenance and chromatin remodeling regulation.
Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Prostate/metabolism , Cell Line, Tumor , Culture Media/chemistry , Gene Expression Profiling , Genomic Instability , Humans , Introns , Male , Neoplasm Invasiveness , Prostate/pathologyABSTRACT
We analyzed microRNA profile in hemolysis-free blood plasma of patients with prostatic cancer. The metastatic form of prostatic cancer was found to be associated with increased levels of hsa-miR-22-3p, hsa-miR-663a, and hsa-miR-4674 in comparison with non-metastatic form. Common candidate target genes of these microRNA include JUNB, KMT2A, and XPO6.
Subject(s)
Biomarkers, Tumor/blood , MicroRNAs/blood , Prostatic Neoplasms, Castration-Resistant/blood , Case-Control Studies , Hemolysis , Humans , Male , Neoplasm Metastasis , Prostatic Neoplasms, Castration-Resistant/pathologyABSTRACT
Peripheral blood plasma profiles of circulating microRNA expression were analyzed in patients with prostatic cancer and benign hyperplasia. In prostatic cancer, significant increase in hsa-miR-619-5p and hsa-miR-1184 microRNA expression and significant decrease in hsalet-7b-5p and hsa-let-7c-5p microRNA expression were observed. The role of the relationship between the microRNA expression and the activities and functions of host genes with introns encoding these microRNA is discussed.
Subject(s)
Biomarkers, Tumor/blood , MicroRNAs/blood , Prostatic Hyperplasia/blood , Prostatic Neoplasms/blood , Diagnosis, Differential , Humans , Male , Prostatic Hyperplasia/diagnosis , Prostatic Neoplasms/diagnosisABSTRACT
Molecule L1CAM is specific for nerve cells and tumors of various localizations. The expression of L1CAM is significantly higher in melanoma in comparison with benign nevi and correlates with the progress of melanoma and transition from radial to vertical growth. Monoclonal antibodies to L1CAM effectively and specifically attenuate melanoma growth, though stimulates the epithelial-mesenchymal transition. shRNA-mediated knock-down of L1CAM showed the involvement of L1CAM in regulation of activity of the canonical Wnt pathway and expression of genes of class I melanoma-associated antigens (MAGE).
Subject(s)
Antigens, Neoplasm/genetics , Neoplasm Proteins/genetics , Neural Cell Adhesion Molecule L1/physiology , Wnt Signaling Pathway , Antigens, Neoplasm/metabolism , Cell Line, Tumor , Gene Expression , Gene Expression Regulation, Neoplastic , Humans , Melanoma/genetics , Melanoma/metabolism , Neoplasm Proteins/metabolismABSTRACT
We analyzed the effect of hemolysis on microRNA profi le of blood plasma. It was found that hemolysis of ~0.05% erythrocytes in a sample signifi cantly affected the concentration of 9 microRNA: hsa-miR-486-5p, hsa-miR-16-5p, hsa-miR-451a, hsa-miR-106a-5p, hsa-miR-17-5p, hsa-miR-93-5p, hsa-miR-20a-5p, hsa-miR-107, and hsa-miR-20b-5p. The effect of hemolysis on plasma content of miR-17 family microRNA was demonstrated.
Subject(s)
MicroRNAs/blood , Biomarkers/blood , Hemoglobins/metabolism , Hemolysis , HumansABSTRACT
Genes with significant differential expression are traditionally used to reveal the genetic background underlying phenotypic differences between cancer cells. We hypothesized that informative marker sets can be obtained by combining genes with a relatively low degree of individual differential expression. We developed a method for construction of highly informative gene combinations aimed at the maximization of the cumulative informative power and identified sets of 2-5 genes efficiently predicting recurrence for ER-positive breast cancer patients. The gene combinations constructed on the basis of microarray data were successfully applied to data acquired by RNA-seq. The developed method provides the basis for the generation of highly efficient prognostic and predictive gene signatures for cancer and other diseases. The identified gene sets can potentially reveal novel essential segments of gene interaction networks and pathways implied in cancer progression.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/genetics , Neoplasm Recurrence, Local/genetics , Transcriptome , Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Gene Regulatory Networks , High-Throughput Nucleotide Sequencing , Humans , Neoplasm Proteins/metabolism , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/pathology , Oligonucleotide Array Sequence Analysis , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolismABSTRACT
We studied the effect of transfection of PC-3 prostate cancer cells with a plasmid encoding shRNA complimentary to a fragment of integrin ß4 (ITGB4). The results attest to considerable changes in the transcriptome of transfected cells. For instance, compensatory changes in the expression of integrin family genes were found.
Subject(s)
Integrin beta4/metabolism , Receptors, Immunologic/metabolism , Receptors, Peptide/metabolism , Animals , Cell Line, Tumor , Gene Expression , Gene Knockdown Techniques , Humans , Integrin beta Chains/genetics , Integrin beta Chains/metabolism , Integrin beta4/genetics , Male , Mice , Neoplasm Transplantation , Prostatic Neoplasms , RNA Interference , RNA, Small Interfering/geneticsABSTRACT
Nuclease resistant extracellular miRNAs have been found in all known biological fluids. The biological function of extracellular miRNAs remains questionable; however, strong evidence suggests that these miRNAs can be more than just byproducts of cellular activity. Some extracellular miRNA species might carry cell-cell signaling function during various physiological and pathological processes. In this review, we discuss the state-of-the-art in the field of intercellular miRNA transport and highlight current theories regarding the origin and the biological function of extracellular miRNAs.
