1. ULK1 inhibition attenuates telomerase activity in hepatic cells.
- Author
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Raza, Sana, Rajak, Sangam, Srivastava, Jyotika, Tewari, Archana, Gupta, Pratima, Chakravarti, Bandana, Ghosh, Sujoy, Chaturvedi, Chandra P., and Sinha, Rohit A.
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TELOMERASE , *LIVER cells , *TELOMERASE reverse transcriptase , *CELLULAR aging , *AUTOPHAGY , *LONGEVITY , *TUMOR growth - Abstract
Autophagy and telomere maintenance are two cellular survival processes that show a strong correlation during human ageing and cancer growth, however, their causal relationship remains unclear. In this study, using an unbiased transcriptomics approach, we uncover a novel role of autophagy genes in regulating telomere extension and maintenance pathways. Concomitantly, the pharmacological inhibition of ULK1 (Unc-51 like autophagy activating kinase 1) attenuated human telomerase reverse transcriptase (hTERT) gene expression and telomerase activity in HepG2 cells. Furthermore, the suppression of telomerase activity upon ULK1 inhibition was associated with telomere shortening and onset of cellular senescence in HepG2 cells. These results, thus, demonstrate a direct role of autophagy in maintaining cellular longevity via regulation of telomerase activity, which may have implications in the pathophysiology of ageing and cancers. • ULK1 inhibition leads to reduced telomerase activity. • ULK1 inhibition promotes onset of cellular senescence. • Autophagy inhibition results in reduced signaling via IL-6-STAT3 pathway regulating hTERT transcription. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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