Na Heya, Li Xiaomeng, Zhang Xinsheng, Xu Yue, Sun Yuzhu, Cui Jingyi, Chen Zihao, Shi Xiaomeng, Ren Shuangyi, Zuo Yunfei
Department of Clinical Biochemistry, Dalian Medical University, Dalian 116044, China; Department of Laboratory Medicine, The People's Hospital of Liaoning Province, Shenyang 110016, China.
Department of Clinical Biochemistry, Dalian Medical University, Dalian 116044, China.
Mol Ther Nucleic Acids. 2020 Sep 4;21:480-491. doi: 10.1016/j.omtn.2020.06.011. Epub 2020 Jun 18.
Previous studies have reported that long noncoding RNAs (lncRNAs) have acted as new players during tumorigenesis. Metallothionein also plays an important role in tumor progression. It is mainly considered to be involved in the process of cell proliferation, oxidative stress, and multidrug resistance. However, the potential involvement of metallothionein-related lncRNAs in colon cancer remains poorly understood. In our study, we found that MT1M affected the expression of lncRNA STEAP3-AS1. STEAP3-AS1 is located in physical contiguity with STEAP3 and notably increased in colon cancer tissues and cell lines. STEAP3-AS1 expression was negatively associated with the expression of STEAP3. High levels of STEPA3-AS1 were associated with poor overall survival in colon cancer patients. In in vitro assays, STEAP3-AS1 knockdown could inhibit colon cancer cell proliferation and migration and arrest colon cancer cells at the G-G phase. In tumorigenicity assays, STEAP3-AS1 knockdown could strongly inhibit tumor growth. Mechanistic investigations demonstrated that STEAP3-AS1 downregulation could increase the expression of cyclin-dependent kinase inhibitor 1C (CDKN1C) by STEAP3 upregulation. Overall, we identify the underlying role of MT1M-related lncRNA STEAP3-AS1 in colon cancer progression, which provides a novel strategy for colon cancer therapy.
先前的研究报道,长链非编码RNA(lncRNAs)在肿瘤发生过程中发挥了新的作用。金属硫蛋白在肿瘤进展中也起着重要作用。它主要被认为参与细胞增殖、氧化应激和多药耐药过程。然而,金属硫蛋白相关lncRNAs在结肠癌中的潜在作用仍知之甚少。在我们的研究中,我们发现MT1M影响lncRNA STEAP3-AS1的表达。STEAP3-AS1与STEAP3在物理上相邻,在结肠癌组织和细胞系中显著增加。STEAP3-AS1的表达与STEAP3的表达呈负相关。高水平的STEPA3-AS1与结肠癌患者较差的总生存期相关。在体外实验中,STEAP3-AS1敲低可抑制结肠癌细胞的增殖和迁移,并使结肠癌细胞停滞在G-G期。在致瘤性实验中,STEAP3-AS1敲低可强烈抑制肿瘤生长。机制研究表明,STEAP3-AS1下调可通过上调STEAP3增加细胞周期蛋白依赖性激酶抑制剂1C(CDKN1C)的表达。总体而言,我们确定了MT1M相关lncRNA STEAP3-AS1在结肠癌进展中的潜在作用,这为结肠癌治疗提供了一种新策略。