Fu Changhao, Chen Kuiqiao, Duan Jinyue, Liu Kun, Li Miaomiao, Chen Yuanyuan, Cong Zhongyi, Wang Yi
Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.
School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
Curr Issues Mol Biol. 2024 Dec 12;46(12):14045-14057. doi: 10.3390/cimb46120840.
Lymphocyte antigen 6 complex, locus K (LY6K) is a putative oncogene in various human cancers, including colorectal cancer, where elevated expression is associated with poor prognosis. This study investigates the antitumor effects of LY6K in colon cancer stem cells (CCSCs) both in vitro and in vivo. EpCAM and CD44 surface markers were used to isolate CCSCs from HCT116 cells, and the expression of LY6K in CCSCs was analyzed by real-time PCR. RNA interference was used to silence LY6K to evaluate its potential role of LY6K on the proliferation, migration, invasion, and cell cycle of CCSCs. Functional assays, including MTS assays, flow cytometric analyses, Transwell migration and invasion assays, and a xenograft model, were used for analysis. The results revealed that LY6K was highly expressed in CCSCs. siRNA-mediated LY6K-silencing in CCSCs inhibited cell proliferation by inducing G1 phase cell cycle arrest and suppressed migration and invasion. In vivo, LY6K silencing effectively reduced tumor growth and extended survival in a mouse model. These findings suggest LY6K as a promising therapeutic target for eradicating CCSCs in colorectal cancer treatment.
淋巴细胞抗原6复合体,K位点(LY6K)是包括结直肠癌在内的多种人类癌症中的一个假定癌基因,其表达升高与预后不良相关。本研究在体外和体内研究了LY6K对结肠癌干细胞(CCSC)的抗肿瘤作用。采用上皮细胞黏附分子(EpCAM)和CD44表面标志物从HCT116细胞中分离CCSC,并通过实时聚合酶链反应(PCR)分析CCSC中LY6K的表达。采用RNA干扰使LY6K沉默,以评估LY6K对CCSC增殖、迁移、侵袭和细胞周期的潜在作用。使用包括MTS检测、流式细胞术分析、Transwell迁移和侵袭检测以及异种移植模型在内的功能检测进行分析。结果显示,LY6K在CCSC中高表达。在CCSC中,小干扰RNA(siRNA)介导的LY6K沉默通过诱导G1期细胞周期阻滞抑制细胞增殖,并抑制迁移和侵袭。在体内,LY6K沉默有效地降低了小鼠模型中的肿瘤生长并延长了生存期。这些发现表明,LY6K是结直肠癌治疗中根除CCSC的一个有前景的治疗靶点。