Dai Xiaoyu, Dong Mingjun, Yu Hua, Xie Yangyang, Yu Yongming, Cao Yisheng, Kong Zhenfang, Zhou Baofeng, Xu Yidong, Yang Tong, Li Keqiang
Department of Anorectal Surgery, Ningbo Second Hospital, Ningbo, Zhejiang, China (mainland).
Clinical Research Center, Ningbo Second Hospital, Ningbo, Zhejiang, China (mainland).
Med Sci Monit. 2017 Jan 26;23:452-461. doi: 10.12659/msm.899595.
BACKGROUND Tectonic family member 1 (TCTN1), a member of the tectonic family, is involved in several developmental processes and is aberrantly expressed in multiple solid tumors. However, the expression and regulation of TCTN1 in human colorectal cancer (CRC) is still not clear. MATERIAL AND METHODS The expression of TCTN1 mRNA was first explored by using Oncomine microarray datasets. TCTN1 expression was silenced in human CRC cell lines HCT116 and SW1116 via RNA interference (RNAi). Furthermore, we investigated the effect of TCTN1 depletion on CRC cell growth by MTT, colony formation, and flow cytometry in vitro. RESULTS In this study, meta-analysis showed that the expressions of TCTN1 mRNA in CRC specimens were significantly higher than that in normal specimens. Knockdown of TCTN1 expression potently inhibited the abilities of cell proliferation and colony formation as determined. Flow cytometry analysis showed that depletion of TCTN1 could cause cell cycle arrest at the G2/M phase. In addition, Annexin V/7-AAD double-staining indicated that TCTN1 silencing promoted cell apoptosis through down-regulation of caspase 3 and Bcl-2 and upregulation of cleaved caspase 3 and PARP. CONCLUSIONS Our results indicate that TCTN1 may be crucial for CRC cell growth, providing a novel alternative to target therapies of CRC. Further research on this topic is warranted.
背景 构造家族成员1(TCTN1)是构造家族的一员,参与多种发育过程,且在多种实体瘤中异常表达。然而,TCTN1在人类结直肠癌(CRC)中的表达及调控仍不清楚。
材料与方法 首先利用Oncomine微阵列数据集探究TCTN1 mRNA的表达情况。通过RNA干扰(RNAi)使TCTN1在人CRC细胞系HCT116和SW1116中沉默。此外,我们在体外通过MTT、集落形成和流式细胞术研究了TCTN1缺失对CRC细胞生长的影响。
结果 在本研究中,荟萃分析表明CRC标本中TCTN1 mRNA的表达显著高于正常标本。如所测定,敲低TCTN1表达可有效抑制细胞增殖和集落形成能力。流式细胞术分析表明,TCTN1缺失可导致细胞周期阻滞在G2/M期。此外,膜联蛋白V/7-AAD双染表明,TCTN1沉默通过下调半胱天冬酶3和Bcl-2以及上调裂解的半胱天冬酶3和PARP促进细胞凋亡。
结论 我们的结果表明,TCTN1可能对CRC细胞生长至关重要,为CRC的靶向治疗提供了一种新的选择。对此主题进行进一步研究是有必要的。