Liu Jie, Zeng Sicong, Wang Yang, Yu Juan, Ouyang Qi, Hu Liang, Zhou Di, Lin Ge, Sun Yi
Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410001, China.
Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha 410001, China.
Stem Cells Int. 2020 Sep 24;2020:5823676. doi: 10.1155/2020/5823676. eCollection 2020.
Human embryonic stem cells (hESCs) gradually accumulate abnormal karyotypes during long-term suboptimal culture, which hinder their application in regenerative medicine. Previous studies demonstrated that the activation of might be implicated in this process. Hence, the hESC line with stably silenced was established to further explore the role of in the malignant transformation of hESCs. It was shown to play a vital role in the maintenance of the physiological properties of stem cells, such as proliferation, migration, differentiation, and telomere regulation. Furthermore, the malignant transformation of hESCs was induced by continuous exposure to 0.001 g/ml mitomycin C (MMC). The results showed that and its target genes, including proto-oncogenes and , were aberrantly upregulated in hESCs after MMC treatment. Moreover, the high expression of accelerated cell transition from G0/G1 phase to the S phase and stimulated the growth of cells containing breakage-fusion-bridge (BFB) cycles. Conversely, silencing inhibited these effects and triggered a survival crisis. The current data indicated that is intimately associated with the physiological properties of stem cells; however, the aberrant expression of is involved in the malignant transformation of hESCs, which might advance the process by facilitating telomere-related unstable cell proliferation. Thus, the aberrant CTNNB1 level might serve as a potential biomarker for detecting the malignant transformation of hESCs.
人类胚胎干细胞（hESCs）在长期的次优培养过程中会逐渐积累异常核型，这阻碍了它们在再生医学中的应用。先前的研究表明，[具体基因名称]的激活可能与这一过程有关。因此，建立了稳定沉默[具体基因名称]的hESC系，以进一步探索[具体基因名称]在hESCs恶性转化中的作用。结果表明，[具体基因名称]在维持干细胞的生理特性，如增殖、迁移、分化和端粒调控等方面起着至关重要的作用。此外，通过持续暴露于0.001 g/ml丝裂霉素C（MMC）诱导hESCs发生恶性转化。结果显示，MMC处理后，[具体基因名称]及其靶基因，包括原癌基因[具体基因名称1]和[具体基因名称2]，在hESCs中异常上调。此外，[具体基因名称]的高表达加速了细胞从G0/G1期向S期的转变，并刺激了含有断裂-融合-桥（BFB）循环的细胞生长。相反，[具体基因名称]的沉默抑制了这些作用，并引发了生存危机。目前的数据表明，[具体基因名称]与干细胞的生理特性密切相关；然而，[具体基因名称]的异常表达参与了hESCs的恶性转化，这可能通过促进与端粒相关的不稳定细胞增殖来推动这一过程。因此，异常的CTNNB1水平可能作为检测hESCs恶性转化的潜在生物标志物。
