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PKMYT1 通过靶向 SIRT3 加剧卵巢癌的进展。

PKMYT1 aggravates the progression of ovarian cancer by targeting SIRT3.

机构信息

Department of Obstetrics and Gynecology, Jinan Second Maternal and Child Health Hospital, Jinan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 May;24(10):5259-5266. doi: 10.26355/eurrev_202005_21308.

DOI:10.26355/eurrev_202005_21308
PMID:32495859
Abstract

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.

摘要

目的

本实验旨在阐明 PKMYT1 在卵巢癌(OC)恶性进展中的作用及其潜在机制。

患者和方法

通过实时定量聚合酶链反应(qRT-PCR)检测 43 对 OC 组织及其相邻正常组织中 PKMYT1 的表达模式。分析 PKMYT1 水平与 OC 患者临床数据的潜在关系。检测 OC 患者是否存在远处转移及其 PKMYT1 水平。通过细胞计数试剂盒(CCK-8)和 Transwell 测定,评估 PKMYT1 对 3AO 和 CAOV3 细胞增殖和转移能力的影响。最后,确定 PKMYT1/SIRT3 调节环在 OC 进展中的作用。

结果

PKMYT1 在 OC 组织中上调,相对于对照。伴有远处转移的 OC 患者 PKMYT1 丰度更高。高水平的 PKMYT1 预示 OC 患者预后不良。PKMYT1 敲低可减弱 OC 细胞的增殖、迁移和侵袭能力。此外,OC 组织中 SIRT3 下调,与 PKMYT1 呈负相关。沉默 SIRT3 可消除 PKMYT1 对 OC 增殖和转移能力的调节作用。

结论

OC 中上调的 PKMYT1 与远处转移和不良预后密切相关。PKMYT1 通过负调控 SIRT3 加速 OC 的恶性进展。

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