The PVT1/miR-612/CENP-H/CDK1 axis promotes malignant progression of advanced endometrial cancer.
Rong Cong, Fanfei Kong, Jian Ma, Qing Li, Hui Yang, Xiaoxin Ma
Abstract
assays. Molecule interactions were illustrated by co-transfection assays. The bioinformatics analysis showed that PVT1/miR-612/CENP-H/CDK1 axis played a vital role in the malignant progression of advanced EC. MiR-612 was downregulated in EC tissues and acted as a tumour suppressor to inhibit cell proliferation, migration, invasion, and promote cell apoptosis. CENP-H was found overexpressed in EC tissues, and the expression level was correlated to diagnosis and prognosis of EC. Hyperactivated CENP-H promoted cell proliferation, migration, invasion, and inhibited cell apoptosis. Overexpressed CENP-H prevented the anti-tumour effects observed with upregulated miR-612; knockdown of miR-612 also suppressed the anti-tumour effects of downregulated PVT1. Knockdown of PVT1 together with upregulated miR-612 exerted the strongest anti-tumour effects in nude mice. These effects were mediated by CDK1 through modulation of the Akt/mTOR signaling pathway. In conclusion, the PVT1/miR-612/CENP-H/CDK1 axis promoted the malignant progression of advanced EC and could serve as a promising target for potential treatments.