ENA0000GenomicsWeizmann Institute of Sciencehttps://www.ebi.ac.uk/ena/browser/view/PRJNA120977Homo sapiensHerpesviruses are known to encode micro (mi)RNAs and to use them to regulate the expression of both viral and cellular genes. The genome of Kaposi’s sarcoma herpesvirus (KSHV) encodes a cluster of twelve miRNAs, which are abundantly expressed during both latency and lytic infection. Relatively few cellular targets of KSHV miRNAs are known. Here, we used a microarray expression profiling approach to analyze the transcriptome of both B lymphocytes and endothelial cells stably expressing KSHV miRNAs and monitor the changes induced by the presence of these miRNAs. We generated a list of potential cellular targets by looking for miRNA seed-match-containing transcripts that were significantly down regulated upon KSHV miRNAs expression. Interestingly, the overlap of putative targets identified in B lymphocytes and endothelial cells was minimal, suggesting a tissue-specific target-regulation by viral miRNAs. Among the putative targets, we identified caspase 3, a critical factor for the control of apoptosis, which we validated using luciferase reporter assays and western blotting. In functional assays we obtained further evidence that KSHV miRNAs indeed protect cells from apoptosis. Overall design: Single-channel hybridization to Affymetrix oligonucleotides microarrays. DG75 and EA.hy926 cells were transducted in triplicates with the K10/12 and K12/12 lentiviral constructs expressing the KSHV miRNAs, or with a GFP-expressing construct as control. The K10/12 construct expressed only the ten intronic miRNAs miR-K12-1 to 9 and miR-K12-11 while the K12/12 construct also expressed miR-K12-10 and miR-K12-12 in addition.ENASarcoma of the Soft Tissue and Bone, MAL NEO SOFT TISSUE NEC, stRNA, caspase-dependent programmed cell death, Spindle Cell Sarcomas, Caspase Dependent Apoptosis, type I programmed cell death, apoptotic programmed cell death, activation of apoptosis, site unspecified, Small, unspecified, Extrinsic Pathway Apoptoses, Soft Tissue Sarcoma, Sarcoma of Soft Tissue, Programmed, Malignant neoplasm of soft tissue, [M]Sarcoma NOS (morphologic abnormality), Type I, tumour of soft tissue and skeleton, Sarcoma of Soft Tissue and Bone, MAL NEO SOFT TIS PELVIS, Malignant neoplasm of connective and other soft tissue of upper limb, Sarcomas, MAL NEO SOFT TIS ABDOMEN, Malignant Tumor of the Soft Tissue, Malignant neoplasm of connective and other soft tissue of head, Small Temporal, MAL NEO SOFT TIS THORAX, Malignant neoplasm of connective and other soft tissue of abdomen, tumor of soft tissue and skeleton, miRNA, Primary miRNA, apoptosis activator activity, pri-miRNA, Intrinsic Pathway Apoptosis, Sarcoma, Malignant neoplasm of soft tissue (disorder), no ICD-O subtype (morphologic abnormality), Classic, Classic Apoptosis, execution phase of apoptotic process, Classical Apoptosis, Malignant tumor of soft tissue, Malignant Neoplasm of the Soft Tissue, face, Spindle Cell Sarcoma, programmed cell death by apoptosis, pre miRNA, connective and soft tissue neoplasm, MAL NEO SOFT TISSUE ARM, MAL NEOPL TRUNK NOS, Apoptosis, Connective Tissue Sarcoma, cellular suicide, Malignant Soft Tissue Tumor, sarcoma, MAL NEO SOFT TISSUE LEG, RNA, cell suicide, Mesenchymal tumor, Caspase-Dependent Apoptosis, malignant, apoptotic cell death, Malignant neoplasm of connective and other soft tissue of lower limb, Small Temporal RNA, Primary, Malignant neoplasm of connective and other soft tissue of thorax, Malignant neoplasm of other specified sites of connective and other soft tissue, [M]Sarcoma NOS, Sarcoma of the Soft Tissue, Malignant neoplasm of connective and other soft tissue, signaling (initiator) caspase activity, Micro RNA, induction of apoptosis, Intrinsic Pathway, including shoulder, Epithelioid Sarcomas, MAL NEO SOFT TISSUE HEAD, Malignant tumour of soft tissue, Programmed Cell Death, Extrinsic Pathway Apoptosis, Soft tissue tumour, NOS, Primary., Caspase-Dependent, Malignant mesenchymal tumour, pre-miRNA, Epithelioid, pri miRNA, apoptosis signaling, Malignant neoplasm of connective and other soft tissue (disorder), miRNAs, Spindle Cell, MAL NEO SOFT TISSUE NOS, apoptosis, Micro, Temporal RNA, including hip, and neck, Soft Tissue Sarcomas, Primary MicroRNA, Malignant neoplasm of connective and other soft tissue of trunk, Cell Death, sarcoma of the soft tissue and bone, Malignant Soft Tissue Neoplasm, Classic Apoptoses, Intrinsic Pathway Apoptoses, no ICD-O subtype, induction of apoptosis by p53, sarcoma of soft tissue and bone, Epithelioid Sarcoma, apoptotic program, mesenchymal tumor, Extrinsic Pathway, commitment to apoptosis, MicroRNA, regulation, Malignant neoplasm of connective and other soft tissue of pelvis, Classical, Apoptoses, Soft Tissuehuman being, human., man0.00.00.00.00.00falseHomo sapiensApoptosis regulation by Kaposi’s sarcoma microRNAs2022-05-122014-02-11PRJNA120977GSE18946221746749606