MicroRNA-622 functions as a tumor suppressor by targeting K-Ras and enhancing the anticarcinogenic effect of resveratrol

Zhiyuan Han, Qiaoyuan Yang, Binbin Liu, Jianjun Wu, Yuanqi Li, Chengfeng Yang, Yiguo Jiang

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

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 G0 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.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalCarcinogenesis
Volume33
Issue number1
DOIs
StatePublished - Jan 2012

Bibliographical note

Funding Information:
National Natural Science Foundation of China (30972443 and 30771780 to J.Y.); the Guangdong Natural Science Foundation (9251018201000004 and 07117550 to J.Y.); the University Talent Program of Guangdong (2010-79 to J.Y.); the Science and Technology Program of Guangzhou (2010Y1-C441 to J.Y.); and the University Talent Program of Guangzhou (10A003D to J.Y.).

ASJC Scopus subject areas

  • Cancer Research

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