TERT Promote Human Laryngeal Carcinoma Cells Proliferation And The Study Of The Relative Mechanism

Background:TERT is the main functional unit of telomerase which maintains telomere length and chromosome structure stability. Recently, TERT has been shown to act as a key factor in many other biological processes, such as cell proliferation, via uncharacterized mechanisms.Methods:We transfected HEp-2laryngeal carcinoma cells with a TERT overexpressing adenovirus (Ad-TERT) and TERT shRNA silencing adenovirus (Ad-sh-TERT), and examined the effect on TERT and the AP-1transcription factor subunits c-Fos and c-Jun using RT-PCR and Western blots. TERT mRNA expression was quantified using RT-PCR in24human laryngeal carcinoma samples, and TERT protein co-expression with AP-1investigated in a human laryngeal carcinoma tissue microarray using quantum-dot based immunofluorescence. The effect of specific ERK and p38inhibitors on ERK, p38, c-Jun and c-Fos phosphorylation was investigated in TERT-overexpressing HEp-2cells.Results:TERT overexpression lead to increased TERT, c-Jun and c-Fos mRNA and protein expression and increased cell proliferation, while TERT silencing had the opposite effects. TERT mRNA expression levels were positively correlated with c-Fos and c-Jun mRNA in human laryngeal carcinoma tissue. TERT and AP-1protein were expressed at high levels and positively correlated in laryngeal carcinoma tissues. Treatment of TERT-overexpressing HEp-2cells with specific p38and ERK inhibitors indicated that TERT modulates expression and phosphorylation of the AP-1subunits c-Jun and c-Fos through the p38and ERK signaling pathways.Conclusion:In conclusion, this study indicates that TERT can promote cell proliferation via activation of the AP-1subunits, c-Jun and c-Fos, in laryngeal carcinoma cells.