miR-34a induces cellular senescence via modulation of telomerase activity in human hepatocellular carcinoma by targeting FoxM1/c-Myc pathway

摘要: // Xinsen Xu 1 , Wei Chen Runchen Miao Yanyan Zhou Zhixin Wang Lingqiang Zhang Yong Wan Yafeng Dong 2 Kai Qu Chang Liu Department of Hepatobiliary Surgery, The First Affiliated Hospital Xi’an Jiaotong University, 710061, China Obstetrics and Gynecology, University Kansas School Medicine, City, KS 66160, USA Correspondence to: Liu, e-mail: liuchangdoctor@163.com Qu, joanne8601@163.com Keywords: miR-34a, HCC, senescence, telomerase, telomere Received: October 07, 2014      Accepted: December 11, Published: January 09, 2015 ABSTRACT Increasing evidence suggests that miRNAs can act as either tumor suppressors or oncogenes in carcinogenesis. In the present study, we identified role miR-34a regulating telomerase activity, with subsequent effect on cellular senescence viability. We found higher expression was significantly correlated advanced clinicopathologic parameters hepatocellular carcinoma. Furthermore, tissues 75 HCC patients demonstrated an inverse correlation between level indices (telomere length activity). Transient introduction into cell lines inhibited activity length, which induced senescence-like phenotypes affected discovered potently targeted c-Myc FoxM1, both were involved activation reverse transcriptase (hTERT) transcription, essential for sustaining to avoid senescence. Taken together, our results demonstrate functions a potent suppressor through modulation pathway