MicroRNA-33b Inhibits Breast Cancer Metastasis by Targeting HMGA2, SALL4 and Twist1

Abstract

MicroRNAs are a class of small noncoding RNAs that regulate gene expression post-transcriptionally either by inhibiting protein translation or by causing the degradation of target mRNAs. Current evidence indicates that miR-33b is involved in the regulation of lipid metabolism, cholesterol homeostasis, glucose metabolism and several human diseases; however, whether miR-33b contributes to the pathogenesis of human cancers and participates in the regulation of self-renewal of human cancer stem cells remains unknown. Here, we report the identification of miR-33b as a negative regulator of cell stemness and metastasis in breast cancer. Compared with paired normal breast tissues, miR-33b expression is downregulated in breast tumor samples and is inversely correlated with lymph node metastatic status. Ectopic overexpression of miR-33b in highly metastatic breast cancer cells suppresses cell self-renewal, migration and invasion in vitro and inhibits lung metastasis in vivo. Conversely, miR-33b knockdown promotes the self-renewal, migration and invasion capabilities of noncancerous mammary epithelial cells. The mechanism through which miR-33b inhibits the stemness, migration and invasion of breast cancer cells is by targeting HMGA2, SALL4 and Twist1. These data indicate that miR-33b acts as an onco-suppressive microRNA in breast cancer progression by inhibiting the stemness and metastasis of breast cancer cells.

SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation

“…Interestingly, we found that levels of miR-33b were reduced in these lipoma samples, suggesting that repression of miR-33b may help promote the overexpression of HMGA2 in some cases of lipoma. These findings are consistent with previous work demonstrating that targeting of HMGA2 by miR-33 regulates proliferation and metastasis of multiple cancer cell lines (47,54,55).…”

“…Although the exact mechanism by which HMGA2 impacts adipocyte clonal expansion and differentiation is not entirely known, it likely involves its ability to control critical genes involved in cellular proliferation. Indeed, HMGA2 is known to be a critical regulator of cell growth in a number of different types of cancer, and regulation of HMGA2 by miR-33 has been shown to regulate proliferation and metastasis in cancer cell lines (47,54,55). We next assessed the proliferative capacity of SGBS cells following stimulation of adipocyte differentiation, and similar to our findings under normal growth conditions, SGBS cells transfected with miR-33b mimics showed reduced capacity for clonal expansion, resulting in significantly reduced cell numbers following 4 days of differentiation (Fig.…”

Anti‐Metastatic and Anti‐Angiogenic Activities of Core–Shell SiO2@LDH Loaded with Etoposide in Non‐Small Cell Lung Cancer

“…The metastatic mouse tumor model was chosen to explore the possible anti‐cancer effect of SiO 2 @LDH‐VP16 28. The effect on anti‐metastasis of SiO 2 @LDH‐VP16, in vivo study was carried out using the tail vein pulmonary model, as shown in Figure 4 .…”

MicroRNAs, a subpopulation of regulators, are involved in breast cancer progression through regulating breast cancer stem cells (Review)

“…HMGA2 (44). miR-888 was identified to act as a repressor of the adherens junction pathway and serve a critical role in maintaining SP properties and regulating EMT, invasion and metastasis in MCF-7 SP cells via directly targeting E-cadherin (45).…”