MEG3 Activated by Vitamin D Inhibits Colorectal Cancer Cells Proliferation and Migration via Regulating Clusterin

Abstract

The long non-coding RNA maternally expressed gene 3 (MEG3) is frequently dysregulated in human cancers; however, its roles in colorectal cancer (CRC) development are largely unknown.

Here, we reported that MEG3 was down-regulated in CRC tissues and CRC patients with lower MEG3 showed poorer overall survival and disease-free survival than those with higher MEG3 level.

MEG3 over-expression represses CRC cells proliferation and migration in vivo and in vitro, while MEG3 knockdown leads to the enhanced proliferation and metastasis of CRC cells. In CRC cells, MEG3 over-expression is related to decreased Clusterin mRNA and the corresponding protein levels, and it also directly binds to Clusterin protein through its 732-1174 region.

In further, Clusterin over-expression rescues the compromised abilities of proliferation and metastasis induced by MEG3 over-expression, suggesting that MEG3 inhibits the CRC progression through regulating the Clusterin activities.

Additionally, we found that 1α,25-(OH)2D and vitamin D receptor (VDR) stimulate MEG3 expression in CRC cells through directly binding to its promoter.

These results suggested that MEG3 functions as a tumor suppressor in CRC via regulating the Clusterin activities and may underlie the anticancer activities of vitamin D on CRC cells. The VDR/MEG3/Clusterin signaling pathway may serve as potential therapeutic targets and prognosis biomarkers for CRC patients in future.

 

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See also:

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