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MiR‐627 mediates the epigenetic mechanism of vitamin D in suppression of colon cancer growth both in vitro and in vivo
Author(s) -
Padi Sathish,
Guo Bin
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1104.5
Subject(s) - calcitriol , in vivo , microrna , cancer research , colorectal cancer , calcitriol receptor , chemistry , in vitro , vitamin d and neurology , cancer , medicine , endocrinology , biology , biochemistry , gene , microbiology and biotechnology
Vitamin D has excellent antitumor activities against various types of cancers, but it cannot be used due to its side effect of causing hypercalcemia. To understand its mechanism of action in tumor suppression, we investigated the effects of Calcitriol (Active form of vitamin D) on microRNA expression in colon cancer cells. We identified miR‐627 as the sole miRNA whose expression was stimulated by calcitriol. Furthermore, JMJD1A (jumonji domain containing 1A) was identified as the target of miR‐627. By downregulating JMJD1A, miR‐627 mediated the effects of calcitriol to increase histone H3K9 ethylation and to suppress the expression of growth and differentiation factor 15 (GDF15). Calcitriol also induced miR‐627 and downregulated JMJD1A in tumor xenografts. Calcitriol significantly suppressed the growth of colon tumors in nude mice, whereas colon tumors with stable JMJD1A‐UTR expression showed resistance to the calcitriol. Overexpression of miR‐627 decreased JMJD1A and suppressed colon cancer growth both in vitro and in vivo in nude mice. We also, found that miR‐627 expression was decreased in human colon cancer specimens when compared to its levels in the normal colon tissues. These results suggest that, miR‐627 and JMJD1A may serve as potential targets to exploit the antitumor activity of vitamin D without eliciting its hypercalcemic side effect. This research is supported by NIH Grants: CA130062 & RR015566