Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells
Abstract Background Renal cell cancer (RCC) is the most common and highly malignant subtype of kidney cancer. Mesenchymal stromal cells (MSCs) are components of tumor microenvironment (TME) that influence RCC progression. The impact of RCC-secreted small non-coding RNAs (sncRNAs) on TME is largely u...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-024-02001-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559236065099776 |
|---|---|
| author | Joanna Bogusławska Małgorzata Grzanka Piotr Popławski Weronika Zarychta-Wiśniewska Anna Burdzinska Karolina Hanusek Helena Kossowska Roksana Iwanicka-Nowicka Alex Białas Beata Rybicka Anna Adamiok-Ostrowska Joanna Życka-Krzesińska Marta Koblowska Leszek Pączek Agnieszka Piekiełko-Witkowska |
| author_facet | Joanna Bogusławska Małgorzata Grzanka Piotr Popławski Weronika Zarychta-Wiśniewska Anna Burdzinska Karolina Hanusek Helena Kossowska Roksana Iwanicka-Nowicka Alex Białas Beata Rybicka Anna Adamiok-Ostrowska Joanna Życka-Krzesińska Marta Koblowska Leszek Pączek Agnieszka Piekiełko-Witkowska |
| author_sort | Joanna Bogusławska |
| collection | DOAJ |
| description | Abstract Background Renal cell cancer (RCC) is the most common and highly malignant subtype of kidney cancer. Mesenchymal stromal cells (MSCs) are components of tumor microenvironment (TME) that influence RCC progression. The impact of RCC-secreted small non-coding RNAs (sncRNAs) on TME is largely underexplored. Here, we comprehensively analysed the composition of exosomal sncRNAs secreted by RCC cells to identify those that influence MSCs. Methods Exosomal sncRNAs secreted by RCC cells and normal kidney cells were analyzed using RNAseq, followed by qPCR validation. MSCs were treated by conditioned media (CM) derived from RCC cells and transfected with piRNA, followed by the analysis of proliferation, viability, migration and immunocytochemical detection of piRNA. Expression of MSCs genes was evaluated using microarray and qPCR. TCGA data were analyzed to explore the expression of sncRNAs in RCC tumors. Results RNAseq revealed 40 miRNAs, 71 tRNAs and four piRNAs that were consistently secreted by RCC cells. qPCR validation using five independent RCC cell lines confirmed that expressions of miR-10b-3p and miR-125a-5p were suppressed, while miR-365b-3p was upregulated in exosomes from RCC cells when compared with normal kidney proximal tubules. The expression of miR-10b-3p and miR-125a-5p was decreased, whereas the expression of miR-365b-3p was increased in RCC tumors and correlated with poor survival of patients. Expressions of tRNA-Glu, tRNA-Gly, and tRNA-Val were the most increased, while tRNA-Gln, tRNA-Leu, and tRNA-Lys were top decreased in RCC exosomes when compared with normal kidney cells. Moreover, hsa_piR_004153, hsa_piR_016735, hsa_piR_019521, and hsa_piR_020365 were consistently upregulated in RCC exosomes. piR_004153 (DQ575660.1; aliases: hsa_piRNA_18299, piR-43772, piR-hsa-5938) was the most highly expressed in exosomes from RCC cells when compared with normal kidney cells. Treatment of MSCs with RCC CM resulted in upregulation of piR_004153 expression. Transfection of MSCs with piR_004153 stimulated their migration and viability, and altered expression of 35 genes, including downregulation of FGF2, SLC7A5, and WISP1. Immunocytochemistry confirmed the nuclear localization of piR_004153 transfected in MSCs. Conclusion RCC cells secrete multiple sncRNAs, including piR_004153 which targets MSCs, alters expression of FGF2, SLC7A5, and WISP1, and stimulates their motility and viability. To our knowledge, this is the first study showing that cancer-derived piRNA can enhance MSC migration. Graphical Abstract |
| format | Article |
| id | doaj-art-b16403d58365458e890ca006965edd95 |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-b16403d58365458e890ca006965edd952025-01-05T12:41:44ZengBMCCell Communication and Signaling1478-811X2025-01-0123111310.1186/s12964-024-02001-1Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cellsJoanna Bogusławska0Małgorzata Grzanka1Piotr Popławski2Weronika Zarychta-Wiśniewska3Anna Burdzinska4Karolina Hanusek5Helena Kossowska6Roksana Iwanicka-Nowicka7Alex Białas8Beata Rybicka9Anna Adamiok-Ostrowska10Joanna Życka-Krzesińska11Marta Koblowska12Leszek Pączek13Agnieszka Piekiełko-Witkowska14Centre of Postgraduate Medical Education, Centre of Translation Research, Department of Biochemistry and Molecular BiologyCentre of Postgraduate Medical Education, Centre of Translation Research, Department of Biochemistry and Molecular BiologyCentre of Postgraduate Medical Education, Centre of Translation Research, Department of Biochemistry and Molecular BiologyDepartment of Clinical Immunology, Medical University of WarsawDepartment of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life SciencesCentre of Postgraduate Medical Education, Centre of Translation Research, Department of Biochemistry and Molecular BiologyLaboratory of Systems Biology, Faculty of Biology, University of WarsawLaboratory of Systems Biology, Faculty of Biology, University of WarsawCentre of Postgraduate Medical Education, Centre of Translation Research, Department of Biochemistry and Molecular BiologyCentre of Postgraduate Medical Education, Centre of Translation Research, Department of Biochemistry and Molecular BiologyCentre of Postgraduate Medical Education, Centre of Translation Research, Department of Biochemistry and Molecular BiologyCentre of Postgraduate Medical Education, Centre of Translation Research, Department of Biochemistry and Molecular BiologyLaboratory of Systems Biology, Faculty of Biology, University of WarsawDepartment of Clinical Immunology, Medical University of WarsawCentre of Postgraduate Medical Education, Centre of Translation Research, Department of Biochemistry and Molecular BiologyAbstract Background Renal cell cancer (RCC) is the most common and highly malignant subtype of kidney cancer. Mesenchymal stromal cells (MSCs) are components of tumor microenvironment (TME) that influence RCC progression. The impact of RCC-secreted small non-coding RNAs (sncRNAs) on TME is largely underexplored. Here, we comprehensively analysed the composition of exosomal sncRNAs secreted by RCC cells to identify those that influence MSCs. Methods Exosomal sncRNAs secreted by RCC cells and normal kidney cells were analyzed using RNAseq, followed by qPCR validation. MSCs were treated by conditioned media (CM) derived from RCC cells and transfected with piRNA, followed by the analysis of proliferation, viability, migration and immunocytochemical detection of piRNA. Expression of MSCs genes was evaluated using microarray and qPCR. TCGA data were analyzed to explore the expression of sncRNAs in RCC tumors. Results RNAseq revealed 40 miRNAs, 71 tRNAs and four piRNAs that were consistently secreted by RCC cells. qPCR validation using five independent RCC cell lines confirmed that expressions of miR-10b-3p and miR-125a-5p were suppressed, while miR-365b-3p was upregulated in exosomes from RCC cells when compared with normal kidney proximal tubules. The expression of miR-10b-3p and miR-125a-5p was decreased, whereas the expression of miR-365b-3p was increased in RCC tumors and correlated with poor survival of patients. Expressions of tRNA-Glu, tRNA-Gly, and tRNA-Val were the most increased, while tRNA-Gln, tRNA-Leu, and tRNA-Lys were top decreased in RCC exosomes when compared with normal kidney cells. Moreover, hsa_piR_004153, hsa_piR_016735, hsa_piR_019521, and hsa_piR_020365 were consistently upregulated in RCC exosomes. piR_004153 (DQ575660.1; aliases: hsa_piRNA_18299, piR-43772, piR-hsa-5938) was the most highly expressed in exosomes from RCC cells when compared with normal kidney cells. Treatment of MSCs with RCC CM resulted in upregulation of piR_004153 expression. Transfection of MSCs with piR_004153 stimulated their migration and viability, and altered expression of 35 genes, including downregulation of FGF2, SLC7A5, and WISP1. Immunocytochemistry confirmed the nuclear localization of piR_004153 transfected in MSCs. Conclusion RCC cells secrete multiple sncRNAs, including piR_004153 which targets MSCs, alters expression of FGF2, SLC7A5, and WISP1, and stimulates their motility and viability. To our knowledge, this is the first study showing that cancer-derived piRNA can enhance MSC migration. Graphical Abstracthttps://doi.org/10.1186/s12964-024-02001-1Renal cell cancerRCCmiRNAtRNApiR_004153piRNA |
| spellingShingle | Joanna Bogusławska Małgorzata Grzanka Piotr Popławski Weronika Zarychta-Wiśniewska Anna Burdzinska Karolina Hanusek Helena Kossowska Roksana Iwanicka-Nowicka Alex Białas Beata Rybicka Anna Adamiok-Ostrowska Joanna Życka-Krzesińska Marta Koblowska Leszek Pączek Agnieszka Piekiełko-Witkowska Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells Cell Communication and Signaling Renal cell cancer RCC miRNA tRNA piR_004153 piRNA |
| title | Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells |
| title_full | Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells |
| title_fullStr | Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells |
| title_full_unstemmed | Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells |
| title_short | Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells |
| title_sort | non coding rnas secreted by renal cancer include pir 004153 that promotes migration of mesenchymal stromal cells |
| topic | Renal cell cancer RCC miRNA tRNA piR_004153 piRNA |
| url | https://doi.org/10.1186/s12964-024-02001-1 |
| work_keys_str_mv | AT joannabogusławska noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT małgorzatagrzanka noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT piotrpopławski noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT weronikazarychtawisniewska noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT annaburdzinska noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT karolinahanusek noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT helenakossowska noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT roksanaiwanickanowicka noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT alexbiałas noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT beatarybicka noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT annaadamiokostrowska noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT joannazyckakrzesinska noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT martakoblowska noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT leszekpaczek noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells AT agnieszkapiekiełkowitkowska noncodingrnassecretedbyrenalcancerincludepir004153thatpromotesmigrationofmesenchymalstromalcells |