Hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP combination results in a good biomarker to distinguish between prostate cancer and non-prostate cancer patients
The incidence and mortality of Prostate Cancer (PCa) worldwide correlate with age and bad dietary habits. Previously, we investigated the mRNA/miRNA role on PCa development and progression using high fat diet (HFD) fed mice. Here our main goal was to investigate the effect of HFD on the expression o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.997457/full |
| _version_ | 1797985885168336896 |
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| author | Rocío Belén Duca Cintia Massillo Paula Lucía Farré Karen Daniela Graña Juana Moro Kevin Gardner Ezequiel Lacunza Adriana De Siervi |
| author_facet | Rocío Belén Duca Cintia Massillo Paula Lucía Farré Karen Daniela Graña Juana Moro Kevin Gardner Ezequiel Lacunza Adriana De Siervi |
| author_sort | Rocío Belén Duca |
| collection | DOAJ |
| description | The incidence and mortality of Prostate Cancer (PCa) worldwide correlate with age and bad dietary habits. Previously, we investigated the mRNA/miRNA role on PCa development and progression using high fat diet (HFD) fed mice. Here our main goal was to investigate the effect of HFD on the expression of PCa-related miRNAs and their relevance in PCa patients. We identified 6 up- and 18 down-regulated miRNAs in TRAMP-C1 mice prostate tumors under HFD conditions using miRNA microarrays. Three down-regulated miRNAs: mmu-miR-133a-3p, -1a-3p and -29c-3p were validated in TRAMP-C1 mice prostate tumor by stem-loop RT-qPCR. Hsa-miR-133a-3p/1-3p expression levels were significantly decreased in PCa compared to normal tissues while hsa-miR-133a-3p was found to be further decreased in metastatic prostate cancer tumors compared to non-metastatic PCa. We examined the promoter region of hsa-miR-133a-3p/1-3p genes and compared methylation at these loci with mature miRNA expression. We found that hsa-miR-1-2/miR-133a-1 cluster promoter hypermethylation decreased hsa-miR-133a-3p/1-3p expression in PCa. GOLPH3 and JUP, two hsa-miR-133a-3p and miR-1-3p predicted target genes, were up-regulated in PCa. ROC analysis showed that the combination of hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP is a promising panel biomarker to distinguish between PCa and normal adjacent tissue (NAT). These results link PCa aggressiveness to the attenuation of hsa-miR-133a-3p and miR-1-3p expression by promoter hypermethylation. Hsa-miR-133a-3p and miR-1-3p down-regulation may enhance PCa aggressiveness in part by targeting GOLPH3 and JUP. |
| first_indexed | 2024-04-11T07:25:28Z |
| format | Article |
| id | doaj.art-77b7ab8c75e64cb4ac091ef2bbb45de7 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T07:25:28Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-77b7ab8c75e64cb4ac091ef2bbb45de72022-12-22T04:37:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.997457997457Hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP combination results in a good biomarker to distinguish between prostate cancer and non-prostate cancer patientsRocío Belén Duca0Cintia Massillo1Paula Lucía Farré2Karen Daniela Graña3Juana Moro4Kevin Gardner5Ezequiel Lacunza6Adriana De Siervi7Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, ArgentinaLaboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, ArgentinaLaboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, ArgentinaLaboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, ArgentinaLaboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, ArgentinaDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, United StatesCentro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Buenos Aires, ArgentinaLaboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, ArgentinaThe incidence and mortality of Prostate Cancer (PCa) worldwide correlate with age and bad dietary habits. Previously, we investigated the mRNA/miRNA role on PCa development and progression using high fat diet (HFD) fed mice. Here our main goal was to investigate the effect of HFD on the expression of PCa-related miRNAs and their relevance in PCa patients. We identified 6 up- and 18 down-regulated miRNAs in TRAMP-C1 mice prostate tumors under HFD conditions using miRNA microarrays. Three down-regulated miRNAs: mmu-miR-133a-3p, -1a-3p and -29c-3p were validated in TRAMP-C1 mice prostate tumor by stem-loop RT-qPCR. Hsa-miR-133a-3p/1-3p expression levels were significantly decreased in PCa compared to normal tissues while hsa-miR-133a-3p was found to be further decreased in metastatic prostate cancer tumors compared to non-metastatic PCa. We examined the promoter region of hsa-miR-133a-3p/1-3p genes and compared methylation at these loci with mature miRNA expression. We found that hsa-miR-1-2/miR-133a-1 cluster promoter hypermethylation decreased hsa-miR-133a-3p/1-3p expression in PCa. GOLPH3 and JUP, two hsa-miR-133a-3p and miR-1-3p predicted target genes, were up-regulated in PCa. ROC analysis showed that the combination of hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP is a promising panel biomarker to distinguish between PCa and normal adjacent tissue (NAT). These results link PCa aggressiveness to the attenuation of hsa-miR-133a-3p and miR-1-3p expression by promoter hypermethylation. Hsa-miR-133a-3p and miR-1-3p down-regulation may enhance PCa aggressiveness in part by targeting GOLPH3 and JUP.https://www.frontiersin.org/articles/10.3389/fonc.2022.997457/fullprostate cancermicroRNAhigh fat dietmethylationoncogenes |
| spellingShingle | Rocío Belén Duca Cintia Massillo Paula Lucía Farré Karen Daniela Graña Juana Moro Kevin Gardner Ezequiel Lacunza Adriana De Siervi Hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP combination results in a good biomarker to distinguish between prostate cancer and non-prostate cancer patients Frontiers in Oncology prostate cancer microRNA high fat diet methylation oncogenes |
| title | Hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP combination results in a good biomarker to distinguish between prostate cancer and non-prostate cancer patients |
| title_full | Hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP combination results in a good biomarker to distinguish between prostate cancer and non-prostate cancer patients |
| title_fullStr | Hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP combination results in a good biomarker to distinguish between prostate cancer and non-prostate cancer patients |
| title_full_unstemmed | Hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP combination results in a good biomarker to distinguish between prostate cancer and non-prostate cancer patients |
| title_short | Hsa-miR-133a-3p, miR-1-3p, GOLPH3 and JUP combination results in a good biomarker to distinguish between prostate cancer and non-prostate cancer patients |
| title_sort | hsa mir 133a 3p mir 1 3p golph3 and jup combination results in a good biomarker to distinguish between prostate cancer and non prostate cancer patients |
| topic | prostate cancer microRNA high fat diet methylation oncogenes |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.997457/full |
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