PKMYT1 aggravates the progression of ovarian cancer by targeting SIRT3

Z.-H. Xuan, H.-P. Wang, X.-N. Zhang, Z.-X. Chen, H.-Y. Zhang, M.-M. Gu

Department of Obstetrics and Gynecology, Jinan Second Maternal and Child Health Hospital, Jinan, China. lwxuanzhenhua@163.com

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• Oncology

OBJECTIVE: This experiment aims to elucidate the role of PKMYT1 in the malignant progression of ovarian cancer (OC) and its underlying mechanism.

PATIENTS AND METHODS: Expression pattern of PKMYT1 in 43 paired OC tissues and adjacent normal ones was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The potential relationship between PKMYT1 level and clinical data of OC patients was analyzed. PKMYT1 level in OC patients either with distant metastasis or not was examined. Through Cell Counting Kit (CCK-8) and transwell assay, influences of PKMYT1 on proliferative and metastatic abilities in 3AO and CAOV3 cells were assessed. At last, the role of PKMYT1/SIRT3 regulatory loop in the progression of OC was identified.

RESULTS: PKMYT1 was upregulated in OC tissues relative to controls. OC patients accompanied with distant metastasis had higher abundance of PKMYT1. High level of PKMYT1 predicted worse prognosis in OC patients. Knockdown of PKMYT1 attenuated proliferative, migratory, and invasive abilities in OC cells. Moreover, SIRT3 was downregulated in OC tissues, which was negatively correlated to PKMYT1. Silencing of SIRT3 could abolish the regulatory effect of PKMYT1 on proliferative and metastatic abilities in OC.

CONCLUSIONS: Upregulated PKMYT1 in OC is closely linked to distant metastasis and poor prognosis. PKMYT1 accelerates the malignant progression of OC via negatively regulating SIRT3.

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