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Tumour-suppressor microRNAs let-7 and mir-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma

Permanent lenke
https://hdl.handle.net/10037/25673
DOI
https://doi.org/10.1038/bjc.2011.220
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article.pdf (519.3Kb)
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Dato
2011-06-07
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Buechner, Jochen; Tømte, Ellen; Haug, Bjørn Helge; Henriksen, Jørn Remi; Løkke, Cecilie; Flægstad, Trond; Einvik, Christer
Sammendrag
BACKGROUND: MicroRNAs (miRNAs) regulate expression of many cancer-related genes through posttranscriptional repression of their mRNAs. In this study we investigate the proto-oncogene MYCN as a target for miRNA regulation.

METHODS: A luciferase reporter assay was used to investigate software-predicted miRNA target sites in the 30 -untranslated region (30 UTR) of MYCN. The miRNAs were overexpressed in cell lines by transfection of miRNA mimics or miRNA-expressing plasmids. Mutation of the target sites was used to validate MYCN 30 UTR as a direct target of several miRNAs. To measure miRNA-mediated suppression of endogenous N-myc protein, inhibition of proliferation and inhibition of clonogenic growth, miRNAs were overexpressed in a MYCN-amplified neuroblastoma cell line.

RESULTS: The results from this study show that MYCN is targeted by several miRNAs. In addition to the previously shown mir-34a/c, we experimentally validate mir-449, mir-19a/b, mir-29a/b/c, mir-101 and let-7e/mir-202 as direct MYCN-targeting miRNAs. These miRNAs were able to suppress endogenous N-myc protein in a MYCN-amplified neuroblastoma cell line. The let-7e and mir-202 were strong negative regulators of MYCN expression. The mir-101 and the let-7 family miRNAs let-7e and mir-202 inhibited proliferation and clonogenic growth when overexpressed in Kelly cells.

CONCLUSION: The tumour-suppressor miRNAs let-7 and mir-101 target MYCN and inhibit proliferation and clonogenic growth of MYCN-amplified neuroblastoma cells.

Forlag
Springer Nature
Sitering
Buechner J, Tømte E, Haug BH, Henriksen JR, Løkke c, Flægstad T, Einvik c. Tumour-suppressor microRNAs let-7 and mir-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma. British Journal of Cancer. 2011;105(2):296-303
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  • Artikler, rapporter og annet (klinisk medisin) [1974]
Copyright 2011 The Author(s)

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