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Gastric cancer is the fourth most common cancer and the second leading cause of cancer mortality worldwide but the underlying molecular mechanism is not entirely clear. The objective of this study was to explore the role of let-7a microRNA (miRNA) in gastric tumorigenesis and the possible correlation between RAB40C and let-7a miRNA in gastric cancer. We found that expression of let-7a is reduced in human gastric cancer tissues and cell lines and there was a significant correlation between the level of let-7a expression and the stage of differentiation. Overexpression of let-7a resulted in a decrease in cell proliferation and G(1) arrest, significantly suppressed anchorage-dependent growth in vitro and the tumorigenicity of gastric cancer cells in a nude mouse xenograft model. Furthermore, we demonstrated that RAB40C is regulated directly by let-7a and plays an essential role as a mediator of the biological effects of let-7a in gastric tumorigenesis. This study revealed that let-7a is significant in suppressing gastric cancer growth in vivo and in vitro and provided the first evidence that RAB40C is negatively regulated by let-7a at the posttranscriptional level via binding to the 3'-untranslated region of RAB40C messenger RNA in gastric cancer. The results of this study suggest that let-7a and RAB40C are potentially useful targets for gastric cancer diagnosis and therapy.

Aberrant expression of microRNA (miRNA) has been previously demonstrated to play an important role in a wide range of cancer types and further elucidation of its role in the mechanisms underlying tumorigenesis, anticarcinogenesis and potential chemotherapeutics is warranted. We chose the anti-benzo[a]pyrene-7,8-diol-9,10-epoxide-transformed human bronchial epithelial cell line 16HBE-T to study miRNAs involved in anticarcinogenesis. In resveratrol-treated cells, we found that miR-622 was upregulated, whereas it was downregulated in 16HBE-T cells, suggesting that miR-622 potentially acts as a tumor suppressor. Increasing the level of miR-622 by transient transfection-induced inhibition of proliferation and G(0) arrest in 16HBE-T cells and the lung cancer cell line H460 as demonstrated by cell viability and cell cycle analysis. MiR-622 dramatically suppressed the ability of 16HBE-T cells to form colonies in vitro and to develop tumors in nude mice. According to bioinformatics analysis, K-Ras messenger RNA was predicted as a putative miR-622 target; this was confirmed by western blot and luciferase reporter assays. Cell growth retardation was inhibited upon knockdown of K-Ras and an increase in the level of miR-622 in 16HBE-T cells. Furthermore, miR-622 inhibitor partially impaired the growth of 16HBE-T cells as demonstrated by luciferase reporter activity and K-Ras protein expression in 16HBE-T cells. In summary, miR-622 functions as a tumor suppressor by targeting K-Ras and impacting the anticancer effect of resveratrol. Therefore, miR-622 is potentially useful as a clinical therapy. MiR-622 impacts the K-Ras signal pathway and the potentially anticarcinogenic or chemotherapeutic properties warrant further investigation.