Telomerase acts as an important biomarker for tumor identification, and synthesizes telomeric repeats at the end of chromosome telomeres during the replicative phase of the cell cycle; thus, the expression level of telomerase changes as the cell cycle progresses. TERT mRNA expression and telomerase activity were significantly increased in over 80% of human cancers from tissue specimens. Although many efforts have been made in detecting the activity of TERT mRNA and active telomerase, the heterogeneous behavior of the cell cycle was overlooked, which might affect the accuracy of the detection results. Herein, the AIEgen-based biosensing systems of PyTPA-DNA and Silole-R were developed to detect the cellular level of TERT mRNA and telomerase in different cell cycles. As a result, the fluorescence signal of cancer cells gradually increased from G0/G1, G1/S to S phase. In contrast, both cancer cells arrested at G2/M phase and normal cells exhibited negligible fluorescence intensities. Compared to normal tissues, malignant tumor samples demonstrated a significant turn-on fluorescence signal. Furthermore, the transcriptomics profiling revealed that tumor biomarkers changed as the cell cycle progressed and biomarkers of CA9, TK1 and EGFR were more abundantly expressed at early S stage. In this vein, our study presented advanced biosensing tools for more accurate analysis of the cell-cycle-dependent activity of TERT mRNA and active telomerase in clinical tissue samples.
端粒酶可作为肿瘤识别的重要生物标志物，在细胞周期复制阶段于染色体端粒末端合成端粒重复序列；因此，端粒酶的表达水平随细胞周期进程而变化。在超过80%的人类癌症组织标本中，TERT mRNA表达和端粒酶活性显著升高。尽管在检测TERT mRNA和活性端粒酶方面已有诸多研究，但细胞周期的异质性行为常被忽视，这可能影响检测结果的准确性。本研究开发了基于AIEgen的PyTPA-DNA和Silole-R生物传感系统，用于检测不同细胞周期中TERT mRNA和端粒酶的细胞水平。结果显示，癌细胞荧光信号从G0/G1期、G1/S期到S期逐渐增强；相反，停滞在G2/M期的癌细胞和正常细胞均表现出可忽略的荧光强度。与正常组织相比，恶性肿瘤样本呈现显著的荧光开启信号。此外，转录组学分析显示肿瘤标志物随细胞周期进程而变化，其中CA9、TK1和EGFR等标志物在S早期表达更丰富。综上，本研究提供了先进的生物传感工具，可更精准分析临床组织样本中TERT mRNA和活性端粒酶的细胞周期依赖性活性。
肿瘤(癌症)患者之家