RNAi mediated silencing of Nanog expression suppresses the growth of human colorectal cancer stem cells
RNAi mediated silencing of Nanog expression suppresses the growth of human colorectal cancer stem cells
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RNAi介导的Nanog表达沉默抑制人结直肠癌干细胞的生长
DOI：
10.1016/j.bbrc.2020.11.101
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发表时间：
2021
影响因子：
3.1
通讯作者：
Wang Yi
中科院分区：
文献类型：
--
作者：
Zhang Chen;Zhao Yuanyuan;Yang Yongjing;Zhong Chunlian;Ji Tianju;Duan Jinyue;Wang Yi
结直肠癌(CRC)是世界上第三常见的癌症，因其无复发预后差而闻名。以前的研究表明，它与癌症干细胞(CSCs)密切相关，CSCs具有自我更新的潜力和分化为不同群体的能力。Nanog是一种重要的转录因子，具有维持胚胎干细胞自我更新和增殖的功能；然而，最近的许多研究表明，Nanog在许多肿瘤干细胞中也有高表达。为了研究Nanog在维持结直肠癌干细胞的干性中是否发挥关键作用，我们利用RNA干扰技术下调了结直肠癌干细胞系EpCAM+CD44+HCT-116干细胞(CCSCs)中Nanog的表达。我们利用小干扰RNA检测了纳米金和玻璃体素的体内抗肿瘤作用。结果表明，CCSCs中Nanog基因的表达水平高于HCT-116细胞。我们发现，缺失Nanog抑制了CCSCs的增殖，促进了细胞的凋亡。此外，当Nanog被小干扰RNA沉默时，CCSCs的侵袭能力明显受到限制。此外，我们还发现，沉默Nanog可以减少肿瘤的大小和重量，并提高荷瘤小鼠的存活率。综上所述，这些发现表明，在结直肠癌干细胞中高表达的Nanog是肿瘤生长过程中的一个关键因素，它可能作为一种潜在的预后标志物和治疗结直肠癌的新的有效靶点。
Colorectal cancer (CRC) is the third most common cancer in the world known for its poor recurrence-free prognosis. Previous studies have shown that it is closely linked with cancer stem cells (CSCs), which have self-renewal potential and the capacity to differentiate into diverse populations. Nanog is an important transcription factor that functions to maintain the self-renewal and proliferation of embryonic stem cells; however, many recent studies have shown that Nanog is also highly expressed in many cancer stem cells. To investigate whether Nanog plays a crucial role in maintaining the stemness of colorectal CSCs, RNA interference was used to downregulate Nanog expression in the CRC stem cell line, EpCAM+CD44+HCT-116 cells (CCSCs). We examined the anti-tumor function of Nanogin vitroandin vivo, using small interfering RNA. Our results revealed that the Nanog mRNA expression level in CCSCs was higher than that in HCT-116 cells. We found that the depletion of Nanog inhibited proliferation and promoted apoptosis in CCSCs. In addition, the invasive ability of CCSCs was markedly restricted when Nanog was silenced by small interfering RNA. Furthermore, we found that the silencing of Nanog decreased tumor size and weight and improved the survival rate of tumor-bearing mice. In conclusion, these findings collectively demonstrate that Nanog, which is highly expressed in CRC stem cells, is a key factor in the development of tumor growth, and it may serve as a potential marker of prognosis and a novel and effective therapeutic target for the treatment of CRC.