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蛋白激酶,膜相关酪氨酸/苏氨酸 1 与结直肠癌的进展相关。

Protein kinase, membrane‑associated tyrosine/threonine 1 is associated with the progression of colorectal cancer.

机构信息

Department of Pathology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam‑do 31151, Republic of Korea.

Soonchunhyang Medical Science Research Institute, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam‑do 31151, Republic of Korea.

出版信息

Oncol Rep. 2018 Jun;39(6):2829-2836. doi: 10.3892/or.2018.6371. Epub 2018 Apr 13.

DOI:10.3892/or.2018.6371
PMID:29658598
Abstract

The protein kinase, membrane‑associated tyrosine/threonine 1 (PKMYT1) is known to inhibit precocious entry into mitosis by phosphorylating CDK1 at Thr14 and Tyr15 residues. However, the functional importance of PKMYT1 in colorectal cancer (CRC) remains unknown. Thus, it is important to elucidate whether PKYMT1 is indispensable in the tumorigenesis of CRC. To investigate the functional importance of PKMYT1 in CRC tumorigenesis, PKMYT1 was knocked down in CRC cell lines such as SW480, SW620, HCT116 and HT29 by siRNA. PKMYT1‑depleted CRC cells were analyzed to determine proliferation, migration, invasion and colony forming ability. In addition, 179 patient‑derived samples were used to find the correlation of the expression of PKMYT1 with the prognosis of CRC patients. By siRNA‑mediated loss of function of PKMYT1, we observed that proliferation, migration, invasion and colony forming ability of CRC cell lines were significantly impaired in the absence of PKMYT1 in vitro. Furthermore, by analyzing patient‑derived samples, we revealed the association of PKMYT1 with the overall survival rate of CRC patients. These results indicated that PKMYT1 plays an essential oncogenic role in CRC and could serve as a good therapeutic target for the treatment of CRC.

摘要

蛋白激酶,膜相关酪氨酸/苏氨酸 1(PKMYT1)通过磷酸化 CDK1 的 Thr14 和 Tyr15 残基来抑制过早进入有丝分裂,这是已知的。然而,PKMYT1 在结直肠癌(CRC)中的功能重要性尚不清楚。因此,阐明 PKYMT1 在 CRC 发生中的必要性非常重要。为了研究 PKMYT1 在 CRC 发生中的功能重要性,通过 siRNA 在 CRC 细胞系(如 SW480、SW620、HCT116 和 HT29)中敲低 PKMYT1。分析 PKMYT1 耗竭的 CRC 细胞以确定增殖、迁移、侵袭和集落形成能力。此外,使用 179 个患者衍生样本确定 PKMYT1 的表达与 CRC 患者预后的相关性。通过 siRNA 介导的 PKMYT1 功能丧失,我们观察到在体外缺乏 PKMYT1 的情况下,CRC 细胞系的增殖、迁移、侵袭和集落形成能力明显受损。此外,通过分析患者衍生样本,我们揭示了 PKMYT1 与 CRC 患者总生存率的关联。这些结果表明,PKMYT1 在 CRC 中发挥着重要的致癌作用,可作为治疗 CRC 的良好治疗靶点。

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