LMTK3 escapes tumour suppressor miRNAs via sequestration of DDX5

Jacob, Jimmy, Favicchio, Rosa, Karimian, Negin, Mehrabi, Maryam, Harding, Victoria, Castellano, Leandro, Stebbing, Justin and Giamas, Georgios (2016) LMTK3 escapes tumour suppressor miRNAs via sequestration of DDX5. Cancer Letters, 372 (1). pp. 137-146. ISSN 0304-3835

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Abstract

Lemur tyrosine kinase-3 (LMTK3) plays an important role in cancer progression and is associated with breast, lung, gastric and colorectal cancer. MicroRNAs (miRNAs) are small endogenous non-coding RNAs that typically repress target genes at post-transcriptional level and have an important role in tumorigenesis. By performing a miRNA expression profile, we identified a subset of miRNAs modulated by LMTK3. We show that LMTK3 induces miR-34a, miR-196-a2 and miR-182 levels by interacting with DEAD-box RNA helicase p68 (DDX5). LMTK3 binds via DDX5 to the pri-miRNA of these three mature miRNAs, thereby sequestrating them from further processing. Ectopic expression of miR-34a and miR-182 in LMTK3-
overexpressing cell lines (MCF7-LMTK3 and MDA-MB-231-LMTK3) inhibits breast cancer proliferation, invasion and migration. Interestingly, miR-34a and miR-182 directly bind to the 3’UTR of LMTK3 mRNA and consequently inhibit both its stability and translation, acting as tumour suppressor-like miRNAs. In aggregate, we show that LMTK3 is involved in miRNA biogenesis through modulation of the Microprocessor complex, inducing miRNAs that target LMTK3 itself.

Item Type: Article
Keywords: LMTK3; DDX5; miR-34a; miR-182; miR-196a; miRNA processing
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Georgios Giamas
Date Deposited: 12 Jan 2016 12:30
Last Modified: 07 Mar 2017 10:10
URI: http://sro.sussex.ac.uk/id/eprint/59108

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