MicroRNA-627 mediates the epigenetic mechanisms of vitamin D to suppress proliferation of human colorectal cancer cells and growth of xenograft tumors in mice.
Gastroenterology
; 145(2): 437-46, 2013 Aug.
Article
in En
| MEDLINE
| ID: mdl-23619147
ABSTRACT
BACKGROUND & AIMS:
Vitamin D protects against colorectal cancer through unclear mechanisms. We investigated the effects of calcitriol (1α,25-dihydroxyvitamin D3; the active form of vitamin D) on levels of different microRNAs (miRNAs) in colorectal cancer cells from humans and xenograft tumors in mice.METHODS:
Expression of miRNAs in colorectal cancer cell lines was examined using the Ambion mirVana miRNA Bioarray. The effects of calcitriol on expression of miR-627 and cell proliferation were determined by real-time polymerase chain reaction and WST-1 assay, respectively; growth of colorectal xenograft tumors was examined in nude mice. Real-time polymerase chain reaction was used to analyze levels of miR-627 in human colon adenocarcinoma samples and nontumor colon mucosa tissues (controls).RESULTS:
In HT-29 cells, miR-627 was the only miRNA significantly up-regulated by calcitriol. Jumonji domain containing 1A (JMJD1A), which encodes a histone demethylase, was found to be a target of miR-627. By down-regulating JMJD1A, miR-627 increased methylation of histone H3K9 and suppressed expression of proliferative factors, such as growth and differentiation factor 15. Calcitriol induced expression of miR-627, which down-regulated JMJD1A and suppressed growth of xenograft tumors from HCT-116 cells in nude mice. Overexpression of miR-627 prevented proliferation of colorectal cancer cell lines in culture and growth of xenograft tumors in mice. Conversely, blocking the activity of miR-627 inhibited the tumor suppressive effects of calcitriol in cultured colorectal cancer cells and in mice. Levels of miR-627 were decreased in human colon adenocarcinoma samples compared with controls.CONCLUSIONS:
miR-627 mediates tumor-suppressive epigenetic activities of vitamin D on colorectal cancer cells and xenograft tumors in mice. The messenger RNA that encodes the histone demethylase JMJD1A is a direct target of miR-627. Reagents designed to target JMJD1A or its messenger RNA, or increase the function of miR-627, might have the same antitumor activities of vitamin D without the hypercalcemic side effects.Key words
1α,25-dihydroxyvitamin D(3); 3' untranslated region; 3'UTR; Apoptosis; BrdU; Cancer Prevention; GDF15; GFP; Gene Regulation; H3K9me2; HIF; JMJD1A; Messenger RNA Processing; PCR; VDR; bromodeoxyuridine; cDNA; calcitriol; complementary DNA; dimethylated lysine 9 of histone H3; green fluorescent protein; growth and differentiation factor 15; hypoxia-inducible transcription factor; jumonji domain containing 1A; mRNA; messenger RNA; miRNA; microRNA; polymerase chain reaction; vitamin D receptor
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vitamins
/
Calcitriol
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Colorectal Neoplasms
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MicroRNAs
/
Epigenesis, Genetic
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Cell Proliferation
Limits:
Animals
/
Humans
Language:
En
Journal:
Gastroenterology
Year:
2013
Document type:
Article
Affiliation country: