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

Abstract

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.

• Authors: Yanping Gao, Longbang Chen, Haizhu Song, Yitian Chen, Rui Wang, Bing Feng
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 19 Pg. 27613-26 (May 10 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27027446 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• E2F3 Transcription Factor
• MIRN200 microRNA, human
• MicroRNAs
• Taxoids
• Docetaxel

Topics

• Adenocarcinoma (drug therapy, genetics, metabolism, pathology)
• Adenocarcinoma of Lung
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Docetaxel
• E2F3 Transcription Factor (genetics, metabolism)
• Humans
• Lung Neoplasms (drug therapy, genetics, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Taxoids (pharmacology)
• Transfection
• Xenograft Model Antitumor Assays