Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
circKDM4C suppresses tumor progression and attenuates doxorubicin resistance by regulating miR-548p/PBLD axis in breast cancer
Ist Teil von
Oncogene, 2019-10, Vol.38 (42), p.6850-6866
Ort / Verlag
England: Nature Publishing Group
Erscheinungsjahr
2019
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Increasing evidence has indicated that circular RNAs (circRNAs) play a critical role in cancer development. However, only a small number of circRNAs have been experimentally validated and functionally annotated. In this study, using a high-throughput microarray assay, we identified a novel circRNA, circKDM4C, which was downregulated in breast cancer tissues with metastasis. Furthermore, we analyzed a cohort of breast cancer patients and found that circKDM4C expression was decreased in breast cancer tissues, and lower circKDM4C expression was associated with poor prognosis and metastasis in breast cancer. Functionally, we demonstrated that circKDM4C significantly repressed breast cancer proliferation, metastasis, and doxorubicin resistance in vitro and in vivo. Mechanistically, using a dual-luciferase activity assay and AGO2 RNA immunoprecipitation, circKDM4C was identified as a miR-548p sponge. We also found that PBLD was a direct target of miR-548p, which functioned as a tumor suppressor in breast cancer. Moreover, miR-548p overexpression was able to reverse the circKDM4C-induced attenuation of malignant phenotypes and elevated expression of PBLD in breast cancer cells. Taken together, our data indicate that circKDM4C might have considerable potential as a prognostic biomarker in breast cancer, and support the notion that therapeutic targeting of circKDM4C/miR-548p/PBLD axis may be a promising treatment approach for breast cancer patients.