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Liver tumor-initiating cells (TICs) are drivers of liver tumorigenesis, and Wnt/β-catenin activation plays a principal role in the self-renewal of liver TICs. Despite a deep understanding of Wnt/β-catenin regulation, the roles of long noncoding RNAs (lncRNAs) in Wnt/β-catenin activation and liver TIC self-renewal are largely unknown. Here, we performed unbiased screening of lncRNAs in liver tumorigenesis and found lncTIC1 was highly expressed with liver tumorigenesis. LncTIC1 was also highly expressed in liver TICs and required for the self-renewal of liver TICs. LncTIC1 drove liver TIC self-renewal through Wnt/β-catenin signaling. LncTIC1 interacted with the N terminal of β-catenin and inhibited the phosphorylation of β-catenin, finally maintaining the stability of β-catenin to drive the activation of Wnt/β-catenin signaling. Through β-catenin maintenance and Wnt/β-catenin regulation, lncTIC1 participated in liver TIC self-renewal, liver tumorigenesis and tumor propagation. Moreover, blockade of lncTIC1 signaling greatly inhibited the propagation of liver cancer and liver TICs.

The effect of Konjac mannan (KM) on spontaneous liver tumorigenesis and fecal flora was studied in C3H/He male mice maintained on a diet containing 10% KM. The weight gain in the 10% KM diet group was lower than that in a control diet group throughout the experimental period. At 12 months of age, the number of liver tumor nodules per mouse in the KM diet group was significantly lower than that in the control diet group (P less than 0.05). Frequency of occurrence of bifidobacteria and bacterial counts of enterobacteriaceae in the KM diet group were significantly higher than those in the control diet group (P less than 0.05). Thus, the present study demonstrates that dietary KM inhibited spontaneous liver tumorigenesis and altered fecal flora in C3H/He male mice.