miR-23b and miR-27b are oncogenic microRNAs in breast cancer: evidence from a CRISPR/Cas9 deletion study

Abstract

Background Altered expression of microRNAs (miRNAs) is known to contribute to cancer progression. miR-23b and miR-27b, encoded within the same miRNA cluster, are reported to have both tumor suppressive and oncogenic activity across human cancers, including breast cancer. Methods To clarify this dichotomous role in breast cancer, miR-23b and miR-27b were knocked out using CRISPR/Cas9 gene knockout technology, and the role of endogenous miR-23b and miR-27b was examined in a breast cancer model system in vitro and in vivo. Results Characterization of the knockout cells in vitro demonstrated that miR-23b and miR-27b are indeed oncogenic miRNAs in MCF7 breast cancer cells. miR-23b and miR-27b knockout reduced tumor growth in xenograft nude mice fed a standard diet, supporting their oncogenic role in vivo. However, when xenograft mice were provided a fish-oil diet, miR-27b depletion, but not miR-23b depletion, compromised fish-oil-induced suppression of xenograft growth, indicating a context-dependent nature of miR-27b oncogenic activity. Conclusions Our results demonstrate that miR-23b and miR-27b are primarily oncogenic in MCF7 breast cancer cells and that miR-27b may have tumor suppressive activity under certain circumstances.

MicroRNA-based regulation of Aurora A kinase in breast cancer

“…MiR-665 expression was also reported to predicts poor survival and promotion of tumor metastasis by targeting NR4A3 in BC [74]. In addition, deletion of CRISPR/Cas9 suggested the oncogenic roles of miR-23b and miR-27b in BC [75]. Mature microRNAs assist AGO by guiding the complex to target sites in mRNAs that are partially complementary to the microRNA sequence (the seed region) [76], and induce repression of gene expression at the level of mRNA stability or translation [77].…”

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

“…For example, oncogenic miRNAs (miR-23 and miR-382) are downregulated by the treatment with sulforaphane [ 94 ]. It has been demystified that knockdown of miR-23 abates the growth of breast cancer in vivo and that miR-382 triggers breast cancer metastasis by activating Ras/ERK signaling pathways via targeting RAS-like estrogen-regulated growth inhibitor (RERG) [ 163 , 164 ] ( Figure 1 and Table 3 ).…”

MicroRNAs in treatment-induced neuroendocrine differentiation in prostate cancer

“…miR-23b and miR-27b cluster is found on human chromosome 9 and has been reported to be downregulated in CRPC tumors [113,114] . miR-23b/27b expression was shown to decrease invasiveness in two independent aggressive CRPC cell lines, ALVA31 and PC3-ML [115] .…”