Knockdown of microRNA-214-3p Promotes Tumor Growth and Epithelial-Mesenchymal Transition in Prostate Cancer

Abnormal expression of microRNA miR-214-3p (miR-214) is associated with multiple cancers. In this study, we assessed the effects of CRISPR/Cas9 mediated miR-214 depletion in prostate cancer (PCa) cells and the underlying mechanisms. Knockdown of miR-214 promoted PCa cell proliferation, invasion, mig...

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Bibliographic Details
Published in:Cancers 2021-11, Vol.13 (23), p.5875
Main Authors: Cagle, Patrice, Smith, Nikia, Adekoya, Timothy O, Li, Yahui, Kim, Susy, Rios-Colon, Leslimar, Deep, Gagan, Niture, Suryakant, Albanese, Christopher, Suy, Simeng, Collins, Sean P, Kumar, Deepak
Format: Article
Language:English
Subjects:
Androgens
Anoikis
Anti-oncogenes
Apoptosis
Cancer therapies
Cell cycle
Cell growth
Cell migration
Cell proliferation
Cloning
CRISPR
E-cadherin
Esophagus
Gene expression
Mesenchyme
Metastases
Metastasis
MicroRNAs
miRNA
N-Cadherin
Ovarian cancer
Prostate cancer
Protein-tyrosine kinase
Therapeutic targets
Tumor suppressor genes
Tumorigenesis
Vimentin
Xenografts
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Summary:Abnormal expression of microRNA miR-214-3p (miR-214) is associated with multiple cancers. In this study, we assessed the effects of CRISPR/Cas9 mediated miR-214 depletion in prostate cancer (PCa) cells and the underlying mechanisms. Knockdown of miR-214 promoted PCa cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and increased resistance to anoikis, a key feature of PCa cells that undergo metastasis. The reintroduction of miR-214 in miR-214 knockdown cells reversed these effects and significantly suppressed cell proliferation, migration, and invasion. These in vitro studies are consistent with the role of miR-214 as a tumor suppressor. Moreover, miR-214 knockout increased tumor growth in PCa xenografts in nude mice supporting its anti-oncogenic role in PCa. Knockdown of miR-214 increased the expression of its target protein, Protein Tyrosine Kinase 6 (PTK6), a kinase shown to promote oncogenic signaling and tumorigenesis in PCa. In addition, miR-214 modulated EMT as exhibited by differential regulation of E-Cadherin, N-Cadherin, and Vimentin both in vitro and in vivo. RNA-seq analysis of miR-214 knockdown cells revealed altered gene expression related to PCa tumor growth pathways, including EMT and metastasis. Collectively, our findings reveal that miR-214 is a key regulator of PCa oncogenesis and is a potential novel therapeutic target for the treatment of the disease.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13235875