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Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells.

Abstract：

BACKGROUND & AIMS:MicroRNAs (miRNAs) can promote or inhibit tumor growth and are therefore being developed as targets for cancer therapies. They are diverse not only in the messenger RNAs (mRNA) they target, but in their production; the same hairpin RNA structure can generate mature products from each strand, termed 5p and 3p, that can bind different mRNAs. We analyzed the expression, functions, and mechanisms of miR-28-5p and miR-28-3p in colorectal cancer (CRC) cells. METHODS:We measured levels of miR-28-5p and miR-28-3p expression in 108 CRC and 49 normal colorectal samples (47 paired) by reverse transcription, quantitative real-time polymerase chain reaction. The roles of miR-28 in CRC development were studied using cultured HCT116, RKO, and SW480 cells and tumor xenograft analyses in immunodeficient mice; their mRNA targets were also investigated. RESULTS:miR-28-5p and miR-28-3p were down-regulated in CRC samples compared with normal colon samples. Overexpression of miRNAs in CRC cells had different effects and the miRNAs interacted with different mRNAs: miR-28-5p altered expression of CCND1 and HOXB3, whereas miR-28-3p bound NM23-H1. Overexpression of miR-28-5p reduced CRC cell proliferation, migration, and invasion in vitro, whereas miR-28-3p increased CRC cell migration and invasion in vitro. CRC cells overexpressing miR-28 developed tumors more slowly in mice compared with control cells, but miR-28 promoted tumor metastasis in mice. CONCLUSION:miR-28-5p and miR-28-3p are transcribed from the same RNA hairpin and are down-regulated in CRC cells. Overexpression of each has different effects on CRC cell proliferation and migration. Such information has a direct application for the design of miRNA gene therapy trials.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Almeida MI,Nicoloso MS,Zeng L,Ivan C,Spizzo R,Gafà R,Xiao L,Zhang X,Vannini I,Fanini F,Fabbri M,Lanza G,Reis RM,Zweidler-McKay PA,Calin GA

doi

10.1053/j.gastro.2011.12.047

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

886-896.e9

issue

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(12)00015-7

journal_volume

142

pub_type

杂志文章

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Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells.