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TLX3 has been established as a sequence-specific transcription factor with vital functions in nervous system.However,its expression,function and down-stream target genes in hepatocellular carcinoma (HCC) remain vague up to now.Hence,in the present investigation,we examined the predictive significance of TLX3 expression in post-surgical HCC patients and sought to reveal its function and underlying molecular mechanisms.Immunohistochemistry assay recruiting 120 pairs of HCC and adjacent liver tissues demonstrated that TLX3 expression was notably down-regulated in HCC tissues and was associated with the longer over-all survival after liver resection.Additionally,there was also a tendency that patients with higher TLX3 expression in HCC tissues had the better recurrence-free survival.Enhanced expression of TLX3 inhibited cell viability and promoted cell apoptosis of HCC cells,whereas silencing TLX3 obtained the opposite results.Transcriptional regulation of PCAF by TLX3 was found by the in vitro experiments including ChIP assay.Taken together,lost expression of TLX3 contributed to PCAF down-regulation in HCC tissues and consequently suppressed HCC progression,which could be a predictive factor for HCC patients after liver resection.