Bladder cancer (BC) is the sixth most common cause of cancer; BC risk increases with age and is m... more Bladder cancer (BC) is the sixth most common cause of cancer; BC risk increases with age and is more common among men than women. Upon diagnosis, the 5-year relative survival rate for patients is approximately 77%. The treatment options available for bladder cancer include chemotherapy, radiation therapy, immunotherapy, targeted therapy, and surgery. Despite the advances in therapeutically novel approaches, BC remains an important problem of public health. Long non-coding RNA (lncRNA) is defined as non-protein-coding RNA molecule longer than 200 nucleotides. Recent findings have highlighted that lncRNA contributes to the regulation of multiple signaling pathways in bladder cancer, suggesting that lncRNA exerts its roles during the biological processes of tumorigenesis, tumor proliferation, differentiation, apoptosis, invasion, migration, and stemness. In our laboratory, we described a family of mitochondrial long non-coding RNAs containing stem-loop structures, named sense and antis...
Background We have previously shown a differential expression of a family of mitochondrial ncRNAs... more Background We have previously shown a differential expression of a family of mitochondrial ncRNAs in normal and cancer cells. Normal proliferating cells and cancer cells express the sense mitochondrial ncRNA (SncmtRNA). In addition, while normal proliferating cells express two antisense mitochondrial ncRNAs (ASncmtRNAs-1 and −2), these transcripts seem to be universally down-regulated in cancer cells. In situ hybridization (ISH) of some normal and cancer tissues reveals nuclear localization of these transcripts suggesting that they are exported from mitochondria. Methods FISH and confocal microscopy, in situ digestion with RNase previous to ISH and electron microscopy ISH was employed to confirm the extra-mitochondrial localization of the SncmtRNA and the ASncmtRNAs in normal proliferating and cancer cells of human and mouse. Results In normal human kidney and mouse testis the SncmtRNA and the ASncmtRNAs were found outside the organelle and especially localized in the nucleus associ...
Amplification of RNA from human sperm heads yielded a fragment of 435 bp that shares 100 % identi... more Amplification of RNA from human sperm heads yielded a fragment of 435 bp that shares 100 % identity with a central region of the 16S mitochondrial rRNA. The nuclear localization in the sperm of the mitochondrial RNA was confirmed by in-situ hybridization. These results, together with the localization of the 16S mitochondrial rRNA in mouse sperm, are the first demonstration that the organelle transcript is a normal component of the mammalian gamete. The possibility that the nuclear mitochondrial RNA arises from nuclear transcription of a mitochondrial pseudogene was ruled out. To determine when during spermatogenesis the mitochondrial RNA is localized in the nucleus, in-situ hybridization of mouse and human testis was carried out. The nuclei of spermatogonia, spermatocytes and round and elongated spermatids were all positively stained. In human spermatocytes, the nuclear staining pattern was fibrillar, suggesting an association of the mitochondrial transcript with the meiotic chromos...
During intercellular communication, cells release extracellular vesicles such as exosomes, which ... more During intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumori...
Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they ... more Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluoresc...
Bladder cancer (BC) is the sixth most common cause of cancer; BC risk increases with age and is m... more Bladder cancer (BC) is the sixth most common cause of cancer; BC risk increases with age and is more common among men than women. Upon diagnosis, the 5-year relative survival rate for patients is approximately 77%. The treatment options available for bladder cancer include chemotherapy, radiation therapy, immunotherapy, targeted therapy, and surgery. Despite the advances in therapeutically novel approaches, BC remains an important problem of public health. Long non-coding RNA (lncRNA) is defined as non-protein-coding RNA molecule longer than 200 nucleotides. Recent findings have highlighted that lncRNA contributes to the regulation of multiple signaling pathways in bladder cancer, suggesting that lncRNA exerts its roles during the biological processes of tumorigenesis, tumor proliferation, differentiation, apoptosis, invasion, migration, and stemness. In our laboratory, we described a family of mitochondrial long non-coding RNAs containing stem-loop structures, named sense and antis...
Background We have previously shown a differential expression of a family of mitochondrial ncRNAs... more Background We have previously shown a differential expression of a family of mitochondrial ncRNAs in normal and cancer cells. Normal proliferating cells and cancer cells express the sense mitochondrial ncRNA (SncmtRNA). In addition, while normal proliferating cells express two antisense mitochondrial ncRNAs (ASncmtRNAs-1 and −2), these transcripts seem to be universally down-regulated in cancer cells. In situ hybridization (ISH) of some normal and cancer tissues reveals nuclear localization of these transcripts suggesting that they are exported from mitochondria. Methods FISH and confocal microscopy, in situ digestion with RNase previous to ISH and electron microscopy ISH was employed to confirm the extra-mitochondrial localization of the SncmtRNA and the ASncmtRNAs in normal proliferating and cancer cells of human and mouse. Results In normal human kidney and mouse testis the SncmtRNA and the ASncmtRNAs were found outside the organelle and especially localized in the nucleus associ...
Amplification of RNA from human sperm heads yielded a fragment of 435 bp that shares 100 % identi... more Amplification of RNA from human sperm heads yielded a fragment of 435 bp that shares 100 % identity with a central region of the 16S mitochondrial rRNA. The nuclear localization in the sperm of the mitochondrial RNA was confirmed by in-situ hybridization. These results, together with the localization of the 16S mitochondrial rRNA in mouse sperm, are the first demonstration that the organelle transcript is a normal component of the mammalian gamete. The possibility that the nuclear mitochondrial RNA arises from nuclear transcription of a mitochondrial pseudogene was ruled out. To determine when during spermatogenesis the mitochondrial RNA is localized in the nucleus, in-situ hybridization of mouse and human testis was carried out. The nuclei of spermatogonia, spermatocytes and round and elongated spermatids were all positively stained. In human spermatocytes, the nuclear staining pattern was fibrillar, suggesting an association of the mitochondrial transcript with the meiotic chromos...
During intercellular communication, cells release extracellular vesicles such as exosomes, which ... more During intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumori...
Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they ... more Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluoresc...
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Papers by Jaime Villegas