The EGFR-induced microRNA miR-7 via Ras/ERK/c-Myc pathway modulates lung cancer oncogenesis by downregulation of ets2-repressor factor, ERF

表皮生長因子接受器(EGFR)誘導微核糖核酸7(miR-7)經Ras/ERK/c-Myc路徑微調肺癌癌化藉由ets2抑制因子(ERF)

林華珩(Hua-Heng Lin)

指導教授 ： 吳成文

國立清華大學/生命科學院/生物科技研究所/碩士(2011年)

https://doi.org/10.6843/NTHU.2011.00265

摘要

MicroRNAs (miRNAs), a novel class of gene regulators, have been associated with tumorigenesis. Aberrant expression and function of epidermal growth factor receptor (EGFR) are reported in most lung cancer cases and are correlated with poor prognosis. Through a miRNA microarray screen for miRNAs regulated by EGFR signaling in lung cancer, we discovered that EGFR induces miR-7 expression. Overexpression of the active EGFR mutant (L858R) enhanced the miR-7 expression. Once transfected in lung cancer cells, Ras and c-Myc promoted miR-7 level; whereas blocking the ERK pathway with inhibitors decreased the miR-7 level, suggesting that the EGFR induces miR-7 expression through the Ras/ERK/c-Myc pathway. Ectopic expression of miR-7 in lung cancer cells promoted cell growth and tumor formation, and significantly increased the mortality of nude mice, indicating miR-7 is an oncomiR. Using a SILAC (stable isotope labeling with amino acids in cell culture) analysis, we found that miR-7 decreases the levels of ERF, suggesting the downstream target of miR-7 is ERF. Furthermore, a miR-7 complementary sequence was identified in the coding sequence of ERF. miR-7 inhibited ectopic expression of the wild-type but not the mutated ERF coding sequence, supporting that ERF is the direct target of miR-7 in lung cancer. Overexpression of miR-7 inhibited ERF expression and rescued ERF-mediated cell growth arrest. Our finding that miR-7 is overexpressed in primary lung cancer and correlated positively with EGFR mutation indicates an important role for miR-7 in the modulation of EGFR-mediated oncogenesis and can serves as a novel biomarker for cancer prognosis.

關鍵字

肺癌 ； 微核醣核酸 ； 表皮生長因子接受器

並列摘要

無資料

並列關鍵字

lung cancer ； miRNA ； EGFR

參考文獻

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