Role and mechanism of ALDH1A1 expression in the development of gastric cancer

ALDH1A1 is one member of the ALDHs gene superfamily locating on human chromosome 9, which oxidizes various aldehydes to the corresponding carboxylic acids. The study aimed to further validate ALDH1A1 expression in gastric cancer tissues and adjacent tissues, and to screen the cell line with highest expression among 6 strains of gastric cancer cell lines and transfected it into gastric cancer cells by the construction of siRNA-ALDH1A1 expression vector. We explored the effect of ALDH1A1 expression on the proliferation, migration and invasion of gastric cancer cells by MTT test, flow cytometry, scratch test and invasive experiments, and detected Wnt/beta-catenin signaling pathway activation by western blot technology. The expression level of the ALDH1A1 in gastric cancer tissue (75.0%, 60/80) was higher than para-carcinoma tissue (38.8%, 31/80) (P<0.05). The cell migration distance in the ALDH1A1 transfection group was longer than that in the control group (42.10 vs. 22.38, P<0.01). The number of gastric cancer cells through the inferior vena in ALDH1A1 transfection group and was more than that in the control group (99.29 vs. 59.37, P<0.05). The siRNA-ALDH1A1 significantly inhibited the expression of Wnt1, Wnt2 and beta-catenin in the gastric cells, the expression of CyclinD1 and PCNA and the expression of MMP-2 & MMP-9 compared to the control group (all P<0.01). ALDH1A1 also up-regulated the expression of E-cadherin and down-regulate the expression of N-cadherin in the gastric cells (P<0.01). In conclusion, interfering ALDH1A1 expression could significantly inhibit the proliferation, migration, invasion and metastasis of MKN-45, and block the cell cycle in phase G1, which were achieved by down-regulating CyclinD1, PCNA, MMP-2, MMP-9 and N-cadherin expression, up-regulating the expression of E-cadherin, and reduce the expressions of Wnt1, Wnt2 and beta-catenin.