Qi Jia, Cui Chunhui, Deng Quanwen, Wang Lifeng, Chen Rihong, Zhai Duanyang, Xie Lang, Yu Jinlong
Department of General Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
Department of Pharmacy, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Oncol Lett. 2018 Nov;16(5):5829-5837. doi: 10.3892/ol.2018.9400. Epub 2018 Sep 5.
Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide, and is difficult to detect in its early stages. Diagnostic and prognostic biomarkers are required, which may also be the basis for improving the targeted therapy for CRC. Sirtuin 6 (SIRT6) is a member of the sirtuin family of gene regulators, which have specific functions in genomic stability, gene transcription and energy metabolism in tumorigenesis. Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is a metabolic enzyme which can be deacetylated by sirtuins. In this study, tissue samples from 29 patients with histologically confirmed CRC of varying grade and stage were studied for SIRT6 and NMNAT2 expression by western blotting and reverse transcription-quantitative polymerase chain reaction. Immunohistochemistry was performed for SIRT6 and NMNAT2 expression in 113 paired (CRC and adjacent) tissue sections. SIRT6 protein and mRNA expression levels were significantly reduced in CRC tissues; NMNAT2 protein and mRNA expression levels were significantly increased in CRC tissues (P<0.01). A negative correlation between the expression of SIRT6 and NMNAT2 in CRC tissue samples was identified (r=-0.246, P<0.01). The reduced expression of SIRT6 and increased expression of NMNAT2 were associated with the tumor depth invasion, stage, differentiation grade (SIRT6 only) and the presence of lymph node metastasis (P<0.05). In conclusion, the findings of the present preliminary study demonstrated that the increased expression of NMNAT2 and reduced expression of SIRT6 may be associated with the progression of CRC. The downregulation of SIRT6 may promote the expression of NMNAT2. Further studies are indicated on the role of NMNAT2 and SIRT6 as potential diagnostic and prognostic biomarkers and as targets for therapy in CRC and other malignant tumors.
结直肠癌（CRC）是全球发病和死亡的重要原因，且在早期难以检测。需要诊断和预后生物标志物，这也可能是改善CRC靶向治疗的基础。沉默调节蛋白6（SIRT6）是基因调节因子沉默调节蛋白家族的成员，其在肿瘤发生过程中的基因组稳定性、基因转录和能量代谢中具有特定功能。烟酰胺单核苷酸腺苷酸转移酶2（NMNAT2）是一种代谢酶，可被沉默调节蛋白去乙酰化。在本研究中，通过蛋白质免疫印迹法和逆转录-定量聚合酶链反应研究了29例组织学确诊的不同分级和分期的CRC患者的组织样本中SIRT6和NMNAT2的表达。对113对（CRC和相邻）组织切片进行了SIRT6和NMNAT2表达的免疫组织化学检测。CRC组织中SIRT6蛋白和mRNA表达水平显著降低；CRC组织中NMNAT2蛋白和mRNA表达水平显著升高（P<0.01）。在CRC组织样本中，SIRT6和NMNAT2的表达之间存在负相关（r=-0.246，P<0.01）。SIRT6表达降低和NMNAT2表达增加与肿瘤深度浸润、分期、分化程度（仅SIRT6）和淋巴结转移的存在相关（P<0.05）。总之，本初步研究结果表明，NMNAT2表达增加和SIRT6表达降低可能与CRC的进展相关。SIRT6的下调可能促进NMNAT2的表达。需要进一步研究NMNAT2和SIRT6作为潜在诊断和预后生物标志物以及CRC和其他恶性肿瘤治疗靶点的作用。
