MicroRNA-622 functions as a tumor suppressor by targeting K-Ras and enhancing the anticarcinogenic effect of resveratrol.
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.
Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, People's Republic of China.
Zhiyuan
Z
Han
Qiaoyuan
Q
Yang
Binbin
B
Liu
Jianjun
J
Wu
Yuanqi
Y
Li
Chengfeng
C
Yang
Yiguo
Y
Jiang
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001980:Bronchi / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D018631:ras Proteins / Q000235:genetics*
D016588:Anticarcinogenic Agents; C117307:KRAS protein, human; C560103:MIRN622 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D013267:Stilbenes; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000077185:Resveratrol