TPP1 Regulates hTERT Expression and Predicts Early Malignant Event and Prognosis of Cervical Cancer

Background: Cervical cancer is one of the most common deadly cancer in women worldwide. However, identifying specific biomarkers is still needed. Telomere-binding protein 1 (TPP1) is vital to telomerase activity. However, the role of TPP1 in cervical cancer and its association with human telomerase reverse transcriptase (hTERT) is unclear.This study aimed at exploring the role of telomere-binding protein 1 (TPP1) in cervical cancer development and progression, and potential mechanisms.Methods: Tissue samples from a total of 274 participants were enrolled for the evaluation of protein expression,156 of whom diagnosed withcervical cancers, 102 with cervical intraepithelial neoplasia (CIN) and 16 with normal cervix. In addition, in vitro cellular models with cervical cancer cell lines Hela, Siha, and C33a were transfected by TPP1-siRNAand protein expression of TPP1 and hTERT were assessed. Results: Compared with normal cervix, TPP1 expression was significantly higher in CIN-III and cervical cancers (P<0.001 for both). High expression of TPP1alone (Plog-rank=0.047)andhigh co-expression of TPP1/hTERT (Plog-rank=0.005)weresignificantly associated with worse survival of cervical cancer patients.After adjusting for well-known prognosis factors, hazard ratio was 2.03(95% confidence interval [CI] 0.99-4.16)for high expression of TPP1 and 2.01(95% CI 1.10-3.67) for high co-expression of TPP1/hTERT. TPP1 and hTERT expressions were positively correlated atall levels of cervical lesions (r=0.524, P<0.001). Knockdown of TPP1 decreased hTERT mRNA and protein expression.Conclusions: High expression of TPP1 might be an early event during cervical cancer development and could be served as apotential prognosis biomarker, especially when used together with hTERT. TPP1 might regulate hTERT expression with detailed underlying mechanisms warrant further investigation.