Hepatocellular carcinoma (HCC) is one of the most common cancerous diseases, with a low 5 year survival rate. Global hypomethylation drives genomic instability, which is regarded as one biomarker for early diagnosis. Long interspersed nucleotide element-1 (LINE-1) makes up around 17% of the genome, and could be regarded as a surrogate marker for global DNA methylation. In this work, a gold nanoparticle (AuNP) modified carbon fiber microelectrode (CFME) with a diameter of 7 μm was applied for the first time to detect the methylation level of LINE-1, by distinguishing adsorption affinities between different DNA bases and AuNPs. Several parameters, including AuNP electrodeposition time, sample adsorption time, and DNA concentration have been analyzed and optimized. The detection limit of our assay was 0.1 nM with only 2 μL sample solution. And the CFME had an excellent sensitivity of 10% methylation change and had the capacity to distinguish only one methylated CpG site. The global DNA methylation level of real samples including cell lines and clinical tissues was tested. Higher signals of HCC cell lines and cancer tissues were observed respectively, compared with normal hepatic cell lines and normal tissues. This work provides a promising approach for HCC early diagnosis and prognosis.
Cardiac aging is a major driver of cardiovascular diseases and associated mortality, yet its therapeutic options are limited. While long interspersed nuclear element-1 (LINE-1) retrotransposons are known to drive cellular senescence, their role in cardiac aging is poorly defined. Here we showed that LINE-1 expression increased in the heart with age. To investigate their role in cardiac aging, we generated cardiomyocyte-specific Mov10 -knockout mice, which failed to suppress LINE-1. These mice developed LINE-1 derepression, cardiac dysfunction and premature cardiac aging by 3 months of age, accompanied by cGAS–STING activation. Pharmacological inhibition of LINE-1 reverse transcription (with 3TC) or STING (with H-151) suppressed cGAS–STING activation and attenuated senescence in Mov10 -knockout H9C2 cells. Notably, both inhibitors improved cardiac function and reduced cardiac inflammation and senescence phenotypes in naturally aged mice. Together, our findings establish LINE-1 as a driver of cardiac aging via cGAS–STING activation, highlighting LINE-1 and its downstream effectors as therapeutic targets for age-related cardiac dysfunction.
危险品化学品经营许可证（带存储）