Up-regulation of miR-24-1-5p is involved in the chemoprevention of colorectal cancer by black raspberry anthocyanins

Abstract

As important epigenetic regulators, microRNA regulate protein expression by triggering the degradation of target mRNA and/or by inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including colorectal cancer. In this study, microRNA-array differential analysis revealed strongly enhanced expression of miR-24-1-5p in the colon tissue of azoxymethane/dextran sulphate sodium-induced mice that were fed with black raspberry anthocyanins for 9 weeks. Overexpression of miR-24-1-5p in human colorectal cancer cells significantly repressed β-catenin expression, and simultaneously decreased cell proliferation, migration and survival. Furthermore, miR-24-1-5p could target β-catenin and trigger a negative regulatory loop for β-catenin and its downstream target genes. β-Catenin signalling is vital to the formation and progression of human colorectal cancer. The current findings therefore identified miR-24-1-5p as a potent regulator of β-catenin, and this may provide a novel chemopreventive and therapeutic strategy for β-catenin signalling-driven colorectal cancer.

Chemopreventive Effect of Dietary Anthocyanins against Gastrointestinal Cancers: A Review of Recent Advances and Perspectives

“…Aberrant expression of micro RNA, a class of small, endogenous, non-coding, single-stranded RNAs that bind to the 3 -untranslated region (3 -UTR) complementary sequences of their target mRNA, plays a critical role in the initiation, promotion, and progression of CRC [225]. Numerous studies have shown that anthocyanins prevent the development of CRC by improving miRNA regulation [226,227]. Exposure to black raspberry anthocyanins results in the overexpression of miR-24-1-5P in the colon tissue of carcinogen-treated mice, leading to significant suppression of β-catenin that in turn reduced CRC cell proliferation and migration, and enhanced survival [226].…”

“…Numerous studies have shown that anthocyanins prevent the development of CRC by improving miRNA regulation [226,227]. Exposure to black raspberry anthocyanins results in the overexpression of miR-24-1-5P in the colon tissue of carcinogen-treated mice, leading to significant suppression of β-catenin that in turn reduced CRC cell proliferation and migration, and enhanced survival [226]. In another study, black raspberry anthocyanins decreased miR-483-3p expression, which is oncogenic in a mouse model of CRC [227].…”

MicroRNA-24 in Cancer: A Double Side Medal With Opposite Properties

“…In CRC, miR-24-3p suppressed cancer cell proliferation, cell migration and invasion, functioning as a tumor suppressor ( 10 ). And miR-24-1-5p decreased CRC cell proliferation, migration and survival significantly by repressing β-catenin expression ( 20 ). Ectopic expression of miR-24 inhibited cell cycle, proliferation, migration, and clonogenic potential of prostate cancer cells, as well as inducing cell apoptosis ( 27 ).…”

“…Moreover, even in the same type of cancer, miR-24 functions oppositely. For example, in colorectal cancer, overexpression of miR-24-1-5p significantly repressed β-catenin expression, and simultaneously decreased CRC cell migration ( 20 ). Michael et al ( 68 ) also confirmed that miR-24 inhibited the cell growth of both lung and colon carcinoma.…”

“…It could suppress NPC cell proliferation, invasion and migration via targeting c-Myc and then regulating epithelial-mesenchymal transition (EMT), indicating that miR-24 might be used as a prognostic factor and as a novel target for the prevention of NPC metastasis ( 19 ). In colorectal cancer, miR-24-1-5p could decrease cell proliferation and migration by repressing β-catenin expression, indicating its role as a tumor suppressor in CRC ( 20 ). However, another study showed that miR-24 was overexpressed in NK (natural killer) cells from CRC patients, compared with healthy volunteers.…”