Research Papers:

A double-negative feedback loop between E2F3b and miR- 200b regulates docetaxel chemosensitivity of human lung adenocarcinoma cells

Yanping Gao, Longbang Chen, Haizhu Song, Yitian Chen, Rui Wang _ and Bing Feng

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Oncotarget. 2016; 7:27613-27626. https://doi.org/10.18632/oncotarget.8376

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Yanping Gao1, Longbang Chen1, Haizhu Song1, Yitian Chen1, Rui Wang1, Bing Feng1

1Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China

Correspondence to:

Rui Wang, email: [email protected]

Bing Feng, email: [email protected]

Keywords: lung adenocarcinoma (LAD), chemoresistance, miR-200b, E2F3b, feedback loop

Received: January 13, 2016     Accepted: March 16, 2016     Published: March 25, 2016


MicroRNAs (miRNAs) are non-coding small RNAs which negatively regulate gene expressions mainly through 3’-untranslated region (3’-UTR) binding of target mRNAs. Recent studies have highlighted the feedback loops between miRNAs and their target genes in physiological and pathological processes including chemoresistance of cancers. Our previous study identified miR-200b/E2F3 axis as a chemosensitivity restorer of human lung adenocarcinoma (LAD) cells. Moreover, E2F3b was bioinformatically proved to be a potential transcriptional regulator of pre-miR-200b gene promoter. The existance of this double-negative feedback minicircuitry comprising E2F3b and miR-200b was confirmed by chromatin immunoprecipitation (ChIP) assay, site-specific mutation and luciferase reporter assay. And the underlying regulatory mechanisms of this feedback loop on docetaxel resistance of LAD cells were further investigated by applying in vitro chemosensitivity assay, colony formation assay, flow cytometric analysis of cell cycle and apoptosis, as well as mice xenograft model. In conclusion, our results suggest that the double-negative feedback loop between E2F3b and miR-200b regulates docetaxel chemosensitivity of human LAD cells mainly through cell proliferation, cell cycle distribution and apoptosis.

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