Abstract | BACKGROUND: METHODS:
RNA sequencing was performed to reveal circRNA expression profiles in ovarian cancerous and normal tissues. Single-molecule RNA in-situ hybridization was used to quantify circPLEKHM3 expression in tumor tissues. Cell-based in-vitro and in-vivo assays were subsequently conducted to support the clinical findings. RESULTS: CircPLEKHM3 was identified as one of the most significantly down-regulated circRNAs in ovarian cancer tissues compared with normal tissues. Its expression was further decreased in peritoneal metastatic ovarian carcinomas compared to primary ovarian carcinomas. Patients with lower circPLEKHM3 tend to have a worse prognosis. Functionally, circPLEKHM3 overexpression inhibited cell growth, migration and epithelial-mesenchymal transition, whereas its knockdown exerted an opposite role. Further analyses showed that circPLEKHM3 sponged miR-9 to regulate the endogenous expression of BRCA1, DNAJB6 and KLF4, and consequently inactivate AKT1 signaling. In addition, AKT inhibitor MK-2206 could block the tumor-promoting effect of circPLEKHM3 depletion, and potentiate Taxol-induced growth inhibition of ovarian cancer cells. CONCLUSIONS:
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Authors | Lei Zhang, Qing Zhou, Qiongzi Qiu, Ling Hou, Mengting Wu, Jia Li, Xufan Li, Bingjian Lu, Xiaodong Cheng, Pengyuan Liu, Weiguo Lu, Yan Lu |
Journal | Molecular cancer
(Mol Cancer)
Vol. 18
Issue 1
Pg. 144
(10 17 2019)
ISSN: 1476-4598 [Electronic] England |
PMID | 31623606
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3' Untranslated Regions
- BRCA1 Protein
- BRCA1 protein, human
- DNAJB6 protein, human
- HSP40 Heat-Shock Proteins
- KLF4 protein, human
- Klf4 protein, mouse
- Kruppel-Like Factor 4
- Lipid-Linked Proteins
- MIRN92 microRNA, human
- MicroRNAs
- Molecular Chaperones
- Nerve Tissue Proteins
- Protein Kinase Inhibitors
- RNA, Circular
- AKT1 protein, human
- Proto-Oncogene Proteins c-akt
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Topics |
- 3' Untranslated Regions
- Animals
- BRCA1 Protein
(genetics)
- Cell Line, Tumor
- Disease Models, Animal
- Female
- Gene Expression Regulation, Neoplastic
- Gene Knockdown Techniques
- Genes, Tumor Suppressor
- HSP40 Heat-Shock Proteins
(genetics)
- Humans
- Immunohistochemistry
- Kruppel-Like Factor 4
- Lipid-Linked Proteins
(genetics)
- Mice
- MicroRNAs
(genetics)
- Models, Biological
- Molecular Chaperones
(genetics)
- Nerve Tissue Proteins
(genetics)
- Ovarian Neoplasms
(genetics, metabolism, mortality, pathology)
- Prognosis
- Protein Kinase Inhibitors
(pharmacology)
- Proto-Oncogene Proteins c-akt
(genetics, metabolism)
- RNA Interference
- RNA, Circular
(genetics)
- Wnt Signaling Pathway
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