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miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression
Background: Ovarian cancer recurrence and metastasis are predominantly attributed to ovarian cancer stem cells; however, the mechanism by which anisomycin regulates human ovarian cancer stem cells (HuOCSCs) remains unclear. Methods: cDNA microArray was used to screen microRNAs (miRNAs) targeted by a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647200/ https://www.ncbi.nlm.nih.gov/pubmed/38021163 http://dx.doi.org/10.7150/jca.87692 |
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author | Ling, Lele Wen, Yichao Chen, Haiyang Xiong, Ying Liu, Xin Chen, Juan Liu, Te Zhang, Bimeng |
author_facet | Ling, Lele Wen, Yichao Chen, Haiyang Xiong, Ying Liu, Xin Chen, Juan Liu, Te Zhang, Bimeng |
author_sort | Ling, Lele |
collection | PubMed |
description | Background: Ovarian cancer recurrence and metastasis are predominantly attributed to ovarian cancer stem cells; however, the mechanism by which anisomycin regulates human ovarian cancer stem cells (HuOCSCs) remains unclear. Methods: cDNA microArray was used to screen microRNAs (miRNAs) targeted by anisomycin, and RT-qPCR validated the miRNA targets. TargetScan database, GO enrichment analysis, and RT-qPCR, accompanied by a fluorescent reporter system, were employed to verify the miRNA target genes. In vitro experimental cell proliferation inhibition assay, flow cytometry, Transwell, angiogenesis assay, and in vivo transplantation tumor assay were implemented to assess the ability of the overexpressed miRNAs to hinder HuOCSC activity. Western blot, RT-qPCR, and immunofluorescence were applied to measure the transcriptional and protein-level expression of the miRNA target genes and their related genes. Bioinformatic analysis predicted and deciphered the role of the miRNA target genes and related genes in the development and prognosis of ovarian cancer. Results: The expression levels of multiple DLK1-DIO3 imprinted microRNA cluster members were altered by anisomycin, among which miR-134-3p expression was most significantly elevated. miR-134-3p overexpression significantly suppressed HuOCSC activity. The screening and validation of target genes uncovered that miR-134-3p was able to markedly suppress GPR137 expression. Additionally, miR-134-3p regulated the cytoskeleton, migration-related protein in the NDEL1/DYNEIN/TUBA1A axis through targeting GPR137. Bioinformatics prediction unveiled a close association of GPR137, NDEL1, DYNC1H1, and TUBA1A with ovarian cancer development and prognosis. Conclusions: The activity of HuOCSCs may be compromised by anisomycin through the regulation of miR-134-3p, which inhibits the GPR137/NDEL1/DYNEIN/TUBA1A axis. |
format | Online Article Text |
id | pubmed-10647200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-106472002023-01-01 miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression Ling, Lele Wen, Yichao Chen, Haiyang Xiong, Ying Liu, Xin Chen, Juan Liu, Te Zhang, Bimeng J Cancer Research Paper Background: Ovarian cancer recurrence and metastasis are predominantly attributed to ovarian cancer stem cells; however, the mechanism by which anisomycin regulates human ovarian cancer stem cells (HuOCSCs) remains unclear. Methods: cDNA microArray was used to screen microRNAs (miRNAs) targeted by anisomycin, and RT-qPCR validated the miRNA targets. TargetScan database, GO enrichment analysis, and RT-qPCR, accompanied by a fluorescent reporter system, were employed to verify the miRNA target genes. In vitro experimental cell proliferation inhibition assay, flow cytometry, Transwell, angiogenesis assay, and in vivo transplantation tumor assay were implemented to assess the ability of the overexpressed miRNAs to hinder HuOCSC activity. Western blot, RT-qPCR, and immunofluorescence were applied to measure the transcriptional and protein-level expression of the miRNA target genes and their related genes. Bioinformatic analysis predicted and deciphered the role of the miRNA target genes and related genes in the development and prognosis of ovarian cancer. Results: The expression levels of multiple DLK1-DIO3 imprinted microRNA cluster members were altered by anisomycin, among which miR-134-3p expression was most significantly elevated. miR-134-3p overexpression significantly suppressed HuOCSC activity. The screening and validation of target genes uncovered that miR-134-3p was able to markedly suppress GPR137 expression. Additionally, miR-134-3p regulated the cytoskeleton, migration-related protein in the NDEL1/DYNEIN/TUBA1A axis through targeting GPR137. Bioinformatics prediction unveiled a close association of GPR137, NDEL1, DYNC1H1, and TUBA1A with ovarian cancer development and prognosis. Conclusions: The activity of HuOCSCs may be compromised by anisomycin through the regulation of miR-134-3p, which inhibits the GPR137/NDEL1/DYNEIN/TUBA1A axis. Ivyspring International Publisher 2023-10-16 /pmc/articles/PMC10647200/ /pubmed/38021163 http://dx.doi.org/10.7150/jca.87692 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Ling, Lele Wen, Yichao Chen, Haiyang Xiong, Ying Liu, Xin Chen, Juan Liu, Te Zhang, Bimeng miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression |
title | miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression |
title_full | miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression |
title_fullStr | miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression |
title_full_unstemmed | miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression |
title_short | miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression |
title_sort | mir-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting gpr137 expression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647200/ https://www.ncbi.nlm.nih.gov/pubmed/38021163 http://dx.doi.org/10.7150/jca.87692 |
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