MiR-7 reduces the BCSC subset by inhibiting XIST to modulate the miR-92b/Slug/ESA axis and inhibit tumor growth

Abstract

Background: Breast cancer stem cells (BCSCs) are typically seed cells of breast tumor that initiate and maintain tumor growth. MiR-7, as a cancer inhibitor, decreases the BCSC subset and inhibits tumor progression through mechanisms that remain unknown. Methods: We examined miR-7 expression in breast cancer and developed a BCSC-driven xenograft mouse model, to evaluate the effects of miR-7 overexpression on the decrease of the BCSC subset in vitro and in vivo. In addition, we determined how miR-7 decreased the BCSC subset by using the ALDEFLUOR, lentivirus infection, dual-luciferase reporter, and chromatin immunoprecipitation-PCR assays. Results: MiR-7 was expressed at low levels in breast cancer tissues compared with normal tissues, and overexpression of miR-7 directly inhibited lncRNA XIST, which mediates the transcriptional silencing of genes on the X chromosome, and reduced epithelium-specific antigen (ESA) expression by increasing miR-92b and inhibiting slug. Moreover, miR-7 suppressed CD44 and ESA by directly inhibiting the NF-κB subunit RELA and slug in breast cancer cell lines and in BCSC-driven xenografts, which confirmed the antitumor activity in mice injected with miR-7 agomir or stably infected with lenti-miR-7. Conclusions: The findings from this study uncover the molecular mechanisms by which miR-7 inhibits XIST, modulates the miR-92b/Slug/ESA axis, and decreases the RELA and CD44 expression, resulting in a reduced BCSC subset and breast cancer growth inhibition. These findings suggest a potentially targeted treatment approach to breast cancer.

Iron Oxide Nanoparticles Combined with Cytosine Arabinoside Show Anti-Leukemia Stem Cell Effects on Acute Myeloid Leukemia by Regulating Reactive Oxygen Species

“…qRT-PCR was performed as previously reported. 35 , 36 Briefly, RNA was extracted from each sample by using a Qiagen RNeasy Kit (Qiagen, Valencia, CA, USA). Concentration of the extracted RNA was measured with Nano Drop ND-1000 Spectrophotometer (Nano Drop Technologies, Thermo Fisher Scientific).…”

Non-coding RNA in cancer

“…Wang et al showed that lncTCF7 was highly expressed in liver cancer stem cells (CSCs) and was important for liver CSC self-renewal [32]. [73] miR-30 promotes apoptosis [76] miR-141 promotes metastasis [74] miR-140 inhibits proliferation [77] mi-766 promotes proliferation, chemoresistance, migration and invasion [75] miR-143 inhibits proliferation [78] miR-600 inhibits stemness [79] miR-7 inhibits cell growth [80] Lung [109] miR-185 impairs survival of drug-resistant cells [110] miR-146a alleviates myeloma proliferation [111] Mechanistically, LncTCF7 recruited SWI/SNF complex to TCF7 promoter and activated Wnt signaling for sustaining liver CSC self-renewal. Epigenetically induced lncRNA1 (EPIC1) is first identified as an oncogene in luminal B breast cancer [33].…”

miRNA signaling networks in cancer stem cells

“…In stemness-enriched cancer cells, miR-205 upregulated by NF-κB signaling suppresses COMMD1 , and then, downregulation of COMMD1 promotes intrinsic and TNF-α-induced inflammatory responses and RelA expression to maintain signaling activation [ 57 ]. RelA promotes CD44 expression but is targeted by the tumor suppressor miR-7-5p [ 58 ]. Previously, we identified that CD44 induces miR-629-3p expression and confers cisplatin resistance [ 59 ].…”