Hcrcn81 promotes cell proliferation through Wnt signaling pathway in colorectal cancer.

Abstract

The objective of the study was to investigate the role of hcrcn81 gene in Wnt/β-catenin signaling pathway related to human colorectal cancer. A total of 30 pairs of human colorectal cancer tissues with control normal tissues were analyzed by qRT-PCR. The proliferation, apoptosis, cell cycle, cell colony and metastasis of LS174T(-hcrcn81), HCT116(-hcrcn81), LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) cells were tested, of which hcrcn81 was knockdown in LS174T, HCT116 cells and hcrcn81 was overexpressed in LoVo, SMMC-7721 cells. Besides, the mRNA and protein levels of hcrcn81, β-catenin, c-Myc, cyclinD1, GSK-3β and survivin in colon cancer cell lines were evaluated by qRT-PCR and western blot. The mRNA levels of β-catenin and Survivin were up-regulated in 76.7% (23/30) and 63.3% (19/30) of the tumor samples, respectively. hcrcn81 and GSK-3β mRNA expression levels were down-regulated in 20/30 (66.7%) and 21/30 (70.0%) of the tumor samples as compared to the adjacent normal tissues, respectively. Furthermore, in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) cells, the mRNA and protein levels of β-catenin, c-Myc, cyclinD1 and Survivin were up-regulated, whereas those of GSK-3 were down-regulated. In LS174T(-hcrcn81) and HCT116(-hcrcn81) cells, the mRNA levels of β-catenin, c-Myc, cyclinD1 and Survivin were down-regulated, whereas GSK-3βmRNA was up-regulated. Cell proliferation in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) groups was significantly enhanced (P<0.05). Proliferation index in both LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) groups was significantly higher than that in the control groups (P<0.05). The number of colony in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) cells were significantly higher than that in the control groups (P<0.05). In addition, the percentage of apoptotic cells in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) groups were significantly lower than that in the control groups (P<0.01, P<0.01). Finally, the number of migrating cells was significantly higher in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) groups than that in the control group (P<0.05). hcrcn81 might promote carcinogenesis and progression through regulation of the Wnt/β-catenin signaling pathway and plays an important role in the carcinogenesis of colorectal cancer.