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A Panel of Eight miRNAs Is Deregulated in HTLV-2 Infected PBMCs and BJABGu Cell Line.

ABSTRACT: Despite human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 being retroviruses closely related at a genomic level, HTLV-2 differs from HTLV-1 in terms of pathogenicity in both single infection and coinfection contexts. Moreover, the HTLV-2 association with clinical outcomes is still debated and several mechanisms underlying HTLV-2 infection remain unexplored as well. Cellular miRNAs are key factors in the post-transcriptional regulation of gene expression and they are known to be potential targets for several pathogens to control the host microenvironment and, in particular, escape immune responses. Here, we identified a HTLV-2-related signature of eight miRNAs (miR-125a-3p, miR-381-3p, miR-502-5p, miR-708-5p, miR-548d-5p, miR-548c-5p, miR-1-3p, and miR-511-5p) in both HTLV-2 infected PBMC and BJABGu cell lines. Altered miRNA expression patterns were correlated with the impairment of Th cell differentiation and signaling pathways driven by cytokines and transcriptional factors such as the Runt-related transcription factor (RUNX) family members. Specifically, we demonstrated that the RUNX2 protein was significantly more expressed in the presence of Tax-2 compared with Tax-1 in an in vitro cell model. To the best of our knowledge, these data represent the first contribution to elucidating the HTLV-2 mediated alteration of host cell miRNA profiles that may impact on HTLV-2 replication and persistent infection.

SUBMITTER: Pilotti E

PROVIDER: S-EPMC9320395 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We investigated the expression profiles of microRNAs (miRNA) in 27 renal cell carcinoma (RCC) FFPE tissues (3 chRCC, 5 papRCC and 18 ccRCC), 4 upper urinary tract-urothelial cell carcinomas of the renal pelvis-ureter (UUT-UCCs) and 20 normal kidneys by using the miRCURY LNAM-bM-^DM-" microRNA Array, 6th gen (Exiqon, Woburn MA), containing capture probes that target all miRNAs for all species registered in the miRBASE version 16.0. Real-time PCR (qRT-PCR) using appropriate endogenous controls was performed in order to validate the microarray results of the 27 most differentially expressed (DE) miRNAs. We identified 434 miRNAs that were significantly deregulated in all kidney tumours compared to the normal tissues. A total of 126 miRNAs (29%) had increased expression while 303 (69.8%) had decreased expression in RCC. Out of the 434 DE miRNAs, we detected 94 co-up-regulated and 218 co-down-regulated microRNAs among chRCC, papRCC and ccRCC. Of these, 89 and 203 were co-up- and co-down-regulated between RCCs and UUT-UCCs, respectively. We detected 11, 44 and 24 up-regulated miRNAs, which were specific for ccRCC, chRCC and papRCC, respectively. Moreover, 19, 18 and 8 miRNAs were uniquelly down-regulated in ccRCC, chRCC and papRCC, respectively. We also detected 89 and 203 co-up- and co-down-regulated miRNAs between kidney cancer and UUT-UCCs. Five miRNAs were up-regulated specifically in renal tumours and 49 in UUT-UCCs, whereas 15 miRNAs were down-regulated specifically in renal tumours and 89 in UUT-UCCs, respectively. Our data validicate that expression of miRNAs tends to be down-regulated renal cell carcinomas compared with normal kidney. We used 18 ccRCC, 3 chRCC, 5 papRCC, 4 UUT-UCC, 1 undifferentiated carcinoma and 19 normal tissue samples for miRNA profiling. Total RNA (0.5 M-BM-5g) from each sample and reference was labeled with Hy3M-bM-^DM-" fluorescent label, using the miRCURY LNAM-bM-^DM-" microRNA Hi-Power Labeling Kit (Exiqon, Woburn MA). The Hy3M-bM-^DM-\"-labeled samples were hybridized to the miRCURY LNAM-bM-^DM-" microRNA Array, 6th gen (Exiqon, Woburn MA), using an Agilent hybridization SureHyb chamber and gasket slide kits. After hybridization, the microarray slides were scanned at 10 M-NM-<m using the High-Resolution Microarray Scanner (Agilent Technologies) and stored in an ozone free environment. The image analysis was carried out using the ImaGene 8.0 software (BioDiscovery, Inc., USA). Raw microarray data were filtered, background corrected and quantile normalizated. Normalized data were further extracted, pre-processed and sorted with Microsoft ExcelM-BM-.. MicroRNAs were considered to be significantly differentially expressed if they obtained a p-value<0.05 and a FDRM-bM-^IM-$0.05.

Project description:BackgroundAfrican-American men with prostate cancer (PCa) present with higher-grade and -stage tumors compared to Caucasians. While the disparity may result from multiple factors, a biological basis is often strongly suspected. Currently, few well-characterized experimental model systems are available to study the biological basis of racial disparity in PCa. We report a validated in vitro cell line model system that could be used for the purpose.MethodsWe assembled a PCa cell line model that included currently available African-American PCa cell lines and LNCaP (androgen-dependent) and C4-2 (castration-resistant) Caucasian PCa cells. The utility of the cell lines in studying the biological basis of variance in a malignant phenotype was explored using a multiplex biomarker panel consisting of proteins that have been proven to play a role in the progression of PCa. The panel expression was evaluated by Western blot and RT-PCR in cell lines and validated in human PCa tissues by RT-PCR. As proof-of-principle to demonstrate the utility of our model in functional studies, we performed MTS viability assays and molecular studies.ResultsThe dysregulation of the multiplex biomarker panel in primary African-American cell line (E006AA) was similar to metastatic Caucasian cell lines, which would suggest that the cell line model could be used to study an inherent aggressive phenotype in African-American men with PCa. We had previously demonstrated that Protein kinase D1 (PKD1) is a novel kinase that is down regulated in advanced prostate cancer. We established the functional relevance by over expressing PKD1, which resulted in decreased proliferation and epithelial mesenchymal transition (EMT) in PCa cells. Moreover, we established the feasibility of studying the expression of the multiplex biomarker panel in archived human PCa tissue from African-Americans and Caucasians as a prelude to future translational studies.ConclusionWe have characterized a novel in vitro cell line model that could be used to study the biological basis of disparity in PCa between African-Americans and Caucasians.

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A Panel of Eight miRNAs Is Deregulated in HTLV-2 Infected PBMCs and BJABGu Cell Line.

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