EGFR promotes lung tumorigenesis by activating miR-7 through a Ras/ERK/Myc pathway that targets the Ets2 transcriptional repressor ERF.

MicroRNAs (miRNA) mediate distinct gene regulatory pathways triggered by epidermal growth factor receptor (EGFR) activation, which occurs commonly in lung cancers with poor prognosis. In this study, we report the discovery and mechanistic characterization of the miRNA miR-7 as an oncogenic "oncomiR" and its role as a key mediator of EGFR signaling in lung cancer cells. EGFR activation or ectopic expression of Ras as well as c-Myc stimulated miR-7 expression in an extracellular signal-regulated kinase (ERK)-dependent manner, suggesting that EGFR induces miR-7 expression through a Ras/ERK/Myc pathway. In support of this likelihood, c-Myc bound to the miR-7 promoter and enhanced its activity. Ectopic miR-7 promoted cell growth and tumor formation in lung cancer cells, significantly increasing the mortality of nude mice hosts, which were orthotopically implanted with lung cancers. Quantitative proteomic analysis revealed that miR-7 decreased levels of the Ets2 transcriptional repression factor ERF, the coding sequence of which was found to contain a miR-7 complementary sequence. Indeed, ectopic miR-7 inhibited production of ERF messages with a wild-type but not a silently mutated coding sequence, and ectopic miR-7 rescued growth arrest produced by wild-type but not mutated ERF. Together, these results identified that ERF is a direct target of miR-7 in lung cancer. Our findings suggest that miR-7 may act as an important modulator of EGFR-mediated oncogenesis, with potential applications as a novel prognostic biomarker and therapeutic target in lung cancer.

Chou YT ，Lin HH ，Lien YC ，Wang YH ，Hong CF ，Kao YR ，Lin SC ，Chang YC ，Lin SY ，Chen SJ ，Chen HC ，Yeh SD ，Wu CW ... -  《-》

Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation.

Cho WC ，Chow AS ，Au JS 《-》

MicroRNA-133b inhibits the growth of non-small-cell lung cancer by targeting the epidermal growth factor receptor.

Both the deregulation of microRNAs and epidermal growth factor receptor (EGFR) are emerging as important factors in non-small-cell lung cancer (NSCLC). Here, miR-133b was found to be associated with tumor stage, the extent of regional lymph node involvement, stage, visceral pleura or vessel invasion and EGFR mRNA expression in Chinese patients with NSCLC. Bioinformatic analysis and luciferase reporter assay revealed that miR-133b can interact specifically with the 3'-UTR of EGFR mRNA. Functionally, miR-133b transfection showed regulatory activity in translationally repressing EGFR mRNA. Moreover, miR-133b transfection may modulate apoptosis, invasion and sensitivity to EGFR-TKI through the EGFR signaling pathways, especially in EGFR-addicted NSCLC cells. Taken together, our findings show that miR-133b can inhibit cell growth of NSCLC through targeting EGFR and regulating its downstream signaling pathway. This finding has important implications for the development of targeted therapeutics for a number of EGFR-addicted cancers.

Liu L ，Shao X ，Gao W ，Zhang Z ，Liu P ，Wang R ，Huang P ，Yin Y ，Shu Y ... -  《-》

Isolation of miRNAs that target EGFR mRNA in human lung cancer.

Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains the leading cause of cancer-related deaths worldwide. Although epidermal growth factor receptor (EGFR) signaling is important and well studied with respect to NSCLC progression, little is known about how miRNAs mediate EGFR signaling to modulate tumorigenesis. To identify miRNAs that target EGFR, we performed a bioinformatics analysis and found that miR-542-5p down-regulates EGFR mRNA and protein expression in human lung cancer cells (H3255, A549, Hcc827). We observed increases in EGFR association with Ago2 in miR-542-5p-transfected cells. Interestingly, we observed an inverse correlation of miR-542-5p expression and EGFR protein levels in human lung cancer tissue samples, suggesting that miR-542-5p directly targets EGFR mRNA. Furthermore, we found that miR-542-5p inhibited the growth of human lung cancer cells. Our findings suggest that miR-542-5p may act as an important modulator of EGFR-mediated oncogenesis, with potential applications as a novel therapeutic target in lung cancer.

Yamaguchi G ，Takanashi M ，Tanaka M ，Fujita K ，Ohira T ，Kuroda M ，Ikeda N ... -  《-》

Prognostic implications of miR-16 expression levels in resected non-small-cell lung cancer.

Navarro A ，Diaz T ，Gallardo E ，Viñolas N ，Marrades RM ，Gel B ，Campayo M ，Quera A ，Bandres E ，Garcia-Foncillas J ，Ramirez J ，Monzo M ... -  《-》