Circ_0000520 contributes to triple-negative breast cancer progression through mediating the miR-1296/ZFX axis.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a high incidence of local recurrence and metastasis. Circular RNAs (circRNAs) are implicated in the pathomechanism of TNBC. Here, we investigated the function of circ_0000520 in TNBC and its associated mechanism. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were used to measure RNA and protein expression. Cell proliferation was analyzed by cell counting kit-8 (CCK8) assay, flow cytometry and colony formation assay. Cell apoptosis was assessed by flow cytometry. Cell migration ability was analyzed by transwell migration and wound healing assays. Transwell invasion assay was conducted to analyze the invasion ability. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pulldown assay were performed to verify the interaction between microRNA-1296 (miR-1296) and circ_0000520 or zinc finger protein X-linked (ZFX). Xenograft mice model was established to analyze the role of circ_0000520 in xenograft tumor growth in vivo. Circ_0000520 expression was upregulated in TNBC tissues and cell lines. Circ_0000520 knockdown suppressed the proliferation, migration, and invasion whereas induced the apoptosis of TNBC cells. miR-1296 was verified as a target of circ_0000520, and circ_0000520 silencing-mediated suppressive effects on the malignant potential of TNBC cells were partly overturned by miR-1296 knockdown. miR-1296 interacted with the 3' untranslated region (3'UTR) of ZFX, and ZFX overexpression partly reversed miR-1296 overexpression-mediated effects in TNBC cells. Circ_0000520 absence reduced ZFX expression by upregulating miR-1296 in TNBC cells. Circ_0000520 silencing suppressed xenograft tumor growth in vivo. Circ_0000520 contributed to TNBC development by binding to miR-1296 to induce ZFX expression.

Zhou Y ，Ma G ，Peng S ，Tuo M ，Li Y ，Qin X ，Yu Q ，Kuang S ，Cheng H ，Li J ... -  《-》

Circ_0041732 regulates tumor properties of triple-negative breast cancer cells by the miR-149-5p/FGF5 pathway.

Li H ，Yin H ，Yan Y 《-》

CircWHSC1 regulates malignancy and glycolysis by the miR-212-5p/AKT3 pathway in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive malignant tumor in breast cancer (BC). Circular RNA circWHSC1 (circWHSC1) is connected with the progression of tumors. However, the role and regulatory mechanism of circWHSC1 in TNBC are unclear. The expression of circWHSC1, microRNA (miR)-212-5p, and protein kinase B-3 (AKT3) mRNA in BC tissues and/or cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The viability, colony formation, migration, invasion, and apoptosis of TNBC cells were determined by cell counting kit-8 (CCK-8), colony formation, transwell, or flow cytometry assays. The levels of glucose consumption and lactate production were assessed with commercial kits. The levels of hexokinase II (HK2) and AKT3 protein were detected by western blotting. The role of circWHSC1 in vivo was verified by tumor xenograft assay. The relationship between miR-212-5p and circWHSC1 or AKT3 was verified via dual-luciferase reporter and RNA pull-down assays. CircWHSC1 was upregulated in BC tissues and cells. Also, circWHSC1 could discriminate BC tissues and paracancerous normal tissues. TNBC patients with high circWHSC1 possessed a poor prognosis. CircWHSC1 silencing reduced TNBC cell growth in vivo and repressed proliferation, migration, invasion, glycolysis, and induced apoptosis of TNBC cells in vitro. CircWHSC1 regulated AKT3 expression by sponging miR-212-5p. Silencing of miR-212-5p overturned circWHSC1 knockdown-mediated impacts on malignancy and glycolysis of TNBC cells. AKT3 overexpression reversed the inhibitory effect of miR-212-5p mimic on malignancy and glycolysis of TNBC cells. CircWHSC1 accelerated malignancy and glycolysis of TNBC cells by the miR-212-5p/AKT3 axis. The research provided a potential prognostic biomarker and therapeutic target for TNBC.

Ding L ，Xie Z 《-》

CCAT1 promotes triple-negative breast cancer progression by suppressing miR-218/ZFX signaling.

Han C ，Li X ，Fan Q ，Liu G ，Yin J ... -  《Aging-US》

Circular RNA circ-ZEB1 acts as an oncogene in triple negative breast cancer via sponging miR-448.

Circular RNAs (circRNAs) play an important role in tumor development. The miRNA sponge is a common role played by circRNAs in various tumors, including breast cancer. This study aimed to explore the role of circ-ZEB1 in the proliferation and apoptosis of triple negative breast cancer (TNBC) cells. The expressions of several circRNAs which were predicted to be bound with miR-448 were detected in 30 clinical TNBC tumor tissues and paired paracancer tissues. The cell counting kit-8 assay was performed to detect the TNBC cell proliferation. The TNBC cell apoptosis was detected using the TUNEL assay. The binding between circ-ZEB1 and miR-448, as well as between miR-448 and eukaryotic elongation factor 2 kinase (eEF2 K), was detected using the RNA pull-down assay and/or the luciferase reporter assay. The effect of circ-ZEB1 knockdown on TNBC tumor growth was detected using the mouse xenograft model. Compared with normal tissues and breast epithelial cells, the expression of circ-ZEB1 was markedly higher in TNBC tumor tissues and tumor cell lines. The small hairpin RNA-mediated circ-ZEB1 knockdown inhibited TNBC cell proliferation and induced cell apoptosis. The RNA pull-down assay and the luciferase reporter assay confirmed the binding between circ-ZEB1 and miR-448, as well as between miR-448 and eEF2 K. The knockdown of circ-ZEB1 was proven to inhibit TNBC cell proliferation and tumor growth via releasing miR-448, and subsequently reducing the expression of the miR-448 target, eEF2 K. In conclusion, our findings identified a new functional circ-ZEB1 in TNBC tumorigenesis, and revealed the important regulatory role of circ-ZEB1 via sponging miR-448, providing a novel insight for TNBC pathogenesis.

Pei X ，Zhang Y ，Wang X ，Xue B ，Sun M ，Li H ... -  《-》