Abstract
BackgroundAltered 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.MethodsTo 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.ResultsCharacterization 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.ConclusionsOur 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.
Highlights
Altered expression of microRNAs 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
Based on the current literature, miR-23b and miR-27b have a dichotomous role in cancer progression. miR-23b expression is down-regulated in human glioma, prostate, bladder, breast, and gastrointestinal cancer, and has been shown to suppress tumor growth, invasion, angiogenesis, and metastasis, and influence chemo-resistance and tumor cell dormancy [6,7,8,9,10,11,12,13,14,15]
While other studies have shown that expression of miR-27b is reduced in lung, prostate, colorectal, gastric, and bladder cancer and it acts as a tumor suppressor by limiting proliferation, inhibiting tumor progression and angiogenesis, and the loss of miR-27b expression promotes epithelial to mesenchymal transition and breast cancer metastasis [9, 24,25,26,27,28]
Summary
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. MiRNAs are predicted to regulate > 90% of protein-coding genes, thereby making them the largest class of gene regulators [1] Due to their broad regulatory role and their various target mRNAs, miRNAs can regulate various normal and pathogenic cellular processes including cell cycle, tumorigenesis, migration/invasion, and angiogenesis functioning as oncogenes or tumor suppressors [2]. While other studies have shown that expression of miR-27b is reduced in lung, prostate, colorectal, gastric, and bladder cancer and it acts as a tumor suppressor by limiting proliferation, inhibiting tumor progression and angiogenesis, and the loss of miR-27b expression promotes epithelial to mesenchymal transition and breast cancer metastasis [9, 24,25,26,27,28]. MiR-23b and miR-27b have been shown to both promote [29, 30] and repress angiogenesis [31,32,33]
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