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The long noncoding RNA HOTTIP has recently been described as a biomarker of poor prognosis in patients with hepatocellular carcinoma (HCC) and pancreatic cancer.In the present study, we evaluated the clinical significance of HOTTIP expression in predicting the rate of tumor recurrence in HCC patients after liver transplantation (LT).We examined the expression of HOTTIP in HCC samples from 155 patients undergoing LT,and its correlation with clinical parameters and tumor recurrence was analyzed.HOTTIP was suppressed using siRNA to explore the role HOTTIP plays in tumor progression.The expression level of HOTTIP in cancer tissues was higher than in adjacent noncancerous tissues.Multivariate analyses revealed that HOTTIP expression was an independent prognostic factor for rumor recurrence in HCC patients after LT (P=0.006, hazard ratio, 1.805).Patients who no longer meet the Milan criteria and exhibit decreased HOTTIP expression experienced longer recurrence-flee survival.Moreover, the suppression of HOTTIP in liver cancer cell lines reduced cell invasion rates and increased chemosensitivity.In summary, the high expression level of HOTTIP in HCC could serve as a candidate biomarker for predicting tumor recurrence in HCC patients undergoing liver transplant therapy.Furthermore, HOTTIP might be a potential therapeutic target.