Knockdown of microRNA-214-3p Promotes Tumor Growth and Epithelial-Mesenchymal Transition in Prostate Cancer.
Patrice CagleNikia SmithTimothy O AdekoyaYahui LiSusy KimLeslimar Rios-ColonGagan DeepSuryakant NitureChristopher AlbaneseSimeng SuySean P CollinsDeepak KumarPublished in: Cancers (2021)
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.
Keyphrases
- cell proliferation
- long non coding rna
- epithelial mesenchymal transition
- prostate cancer
- long noncoding rna
- induced apoptosis
- gene expression
- poor prognosis
- cell cycle
- tyrosine kinase
- rna seq
- crispr cas
- single cell
- cell cycle arrest
- endoplasmic reticulum stress
- signaling pathway
- type diabetes
- radical prostatectomy
- cell death
- metabolic syndrome
- risk assessment
- adipose tissue
- skeletal muscle
- oxidative stress
- genome editing
- genome wide
- high fat diet induced