Ubiquitous mitochondrial creatine kinase regulates cell proliferation and metastasis in colorectal cancer （CRC） by targeting PI3K/AKT/mTOR signaling pathway

doi:10.3969/j.issn.1009-976X.2021.05.009

Abstract

Abstract: Objective Ubiquitous mitochondrial creatine kinase （uMtCK） plays an important role in the occurrence and progression of tumor. In this study, we aimed to clarify the potential role and regulatory mechanism of uMtCK in colorectal cancer （CRC）. Methods We detected the expression levels of uMtCK in CRC tissues of our center, using quantitative real-time polymerase chain reaction. uMtCK downregulated CRC cells were constructed using siRNA transfection, and then cell proliferation, metastasis capacities and related pathways were identified by Cell Counting Kit-8, Transwell and Western blot, respectively. Results Our data showed that uMtCK was overexpressed in CRC tissues in contrast to adjacent nontumor tissues, and the relative expression levels of uMtCK were closely associated with T classification （P=0.002）, N stage （P=0.000）, TNM stage （P=0.000） and disease-free rates. In addition, downregulation of uMtCK could significantly suppress proliferation, inhibit migration and invasion, and reverse PI3K/AKT/mTOR signaling pathway. Conclusion uMtCK enhanced the proliferation and metastasis of CRC cells by regulating PI3K/AKT/mTOR signaling pathway, and uMtCK might be a prospective target of CRC therapy.

Key words: colorectal cancer, uMtCK, proliferation, metastasis, PI3K/AKT/mTOR

摘要： 目的广泛型线粒体肌酸激酶（uMtCK）基因在肿瘤的中发生和发展中起着重要作用,目前uMtCK在结直肠癌进展中的作用仍不清楚。本研究旨在阐明uMtCK在结直肠癌发生中的潜在作用和调控机制。方法荧光定量PCR验证uMtCK在本中心结直肠癌生物样本库中的表达水平。小分子RNA敲低结直肠癌细胞内uMtCK表达,通过CCK-8增殖实验、Transwell和Westernblot检测uMtCK对结直肠癌细胞增殖、迁移及转移能力的影响及潜在的调控机制。结果与邻近正常组织相比,uMtCK在结直肠癌组织中呈高表达,其表达与T分期（P=0.002）、N分期（P=0.002）、TNM分期（P=0.000）和无瘤生存率密切相关。下调uMtCK的表达可显著抑制增殖能力、降低迁移和侵袭能力,同时逆转PI3K/AKT/mTOR信号通路。结论 uMtCK通过调节PI3K/AKT/mTOR信号通路调控结直肠癌细胞增殖及转移能力,是结直肠癌的潜在治疗靶点。

关键词: 结直肠癌, uMtCK, 增殖, 转移, PI3K/AKT/mTOR信号通路

CLC Number:

TANG Xing-kui, LIN Yu-kun, HE Jia-lin, LUO Xi-jun, LIANG Jun-jie, ZHU Xian-jun. Ubiquitous mitochondrial creatine kinase regulates cell proliferation and metastasis in colorectal cancer （CRC） by targeting PI3K/AKT/mTOR signaling pathway[J]. Lingnan Modern Clinics In Surgery, 2021, 21(05): 535-540.

唐兴奎, 林玉坤, 何嘉琳, 罗喜俊, 梁俊杰, 朱显军. 广泛型线粒体肌酸激酶基因在结直肠癌中的表达及生物学意义[J]. 岭南现代临床外科, 2021, 21(05): 535-540.

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