circ_0089153 exacerbates breast cancer cells proliferation and metastasis via sponging miR-2467-3p/E2F6.

The role of circ_0089153 in breast cancer (BCa) malignancy development was explored. circ_0089153 expression in BCa was analyzed by Gene Expression Omnibus database. Clinical tissues were obtained from 90 BCa patients. Cell counting kit-8 assay, 5-ethnyl-2 deoxyuridine assay and colony formation experiment were applied for proliferation detection. Wound healing assay and Transwell experiment were used for migration and invasion detection. Dual luciferase reporter gene assay, RNA immunoprecipitation assay and RNA pull-down assay were conducted. In vivo growth and metastasis of BCa cells were performed. Quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were applied for RNAs and proteins expression. The up-modulated circ_0089153 indicated an unfavorable survival of BCa patients. circ_0089153 knockdown attenuated BCa cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) (P < .01). circ_0089153 was miR-2467-3p sponge. Low miR-2467-3p expression indicated a worse survival of BCa patients. miR-2467-3p overexpression reduced BCa cells proliferation, migration, invasion and EMT (P < .05). circ_0089153 enhanced BCa cells proliferation, migration, invasion and EMT by sponging miR-2467-3p (P < .05). E2F6 was directly suppressed by miR-2467-3p. E2F6 high expression in BCa patients associated with worse survival. circ_0089153 knockdown suppressed in vivo BCa cells growth and lung metastasis (P < .01). circ_0089153 was an oncogene in breast cancer, which enhanced proliferation and metastasis through sponging miR-2467-3p/E2F6. circ_0089153 was suggested to be a potential target for BCa target treatment.

Gao SL ，Fan Y ，Liu XD ，Liu W ，Zhao M ... -  《-》

Knockdown of circ_0006528 Suppresses Cell Proliferation, Migration, Invasion, and Adriamycin Chemoresistance via Regulating the miR-1236-3p/CHD4 Axis in Breast Cancer.

Adriamycin (ADM) is one of the postoperative chemotherapy drugs for breast cancer (BCa) patients. Circular RNAs have been shown to modulate ADM resistance in many cancers. However, it is unclear whether circ_0006528 can modulate the ADM chemoresistance in BCa. Levels of circ_0006528, microRNA-1236-3p (miR-1236-3p), and chromodomain helicase DNA-binding protein 4 (CHD4) were detected by quantitative real-time polymerase chain reaction or western blot. Cell proliferation, the half maximal inhibitory concentration (IC50) value of ADM, and cell migration and invasion were evaluated by cell counting kit-8 and transwell assays, respectively. The interaction among circ_0006528, miR-1236-3p, and CHD4 was confirmed using dual-luciferase reporter assays. Tumor formation in nude mice was performed to explore the effect of circ_0006528 in vivo. Higher levels of circ_0006528 and CHD4 and lower level of miR-1236-3p were found in ADM-resistant BCa tissues and cells, and patients with high circ_0006528 had a shorter overall survival. Circ_0006528 could directly bind to miR-1236-3p, and circ_0006528 knockdown or miR-1236-3p overexpression could suppress cell proliferation, migration, invasion, and ADM resistance in ADM-resistant BCa cells. Moreover, circ_0006528-regulated CHD4 expression by sponging miR-1236-3p, and CHD4 elevation reversed the inhibitory effect of circ_0006528 knockdown on ADM-resistant BCa cells. Consistently, circ_0006528 inhibition retarded ADM-resistant BCa tumor growth in vivo by decreasing CHD4 and increasing miR-1236-3p. Downregulation of circ_0006528 restrained cell proliferation, migration, invasion, and drug resistance of ADM-resistant BCa cells through inhibiting CHD4 and inducing miR-1236-3p.

Hao J ，Du X ，Lv F ，Shi Q ... -  《-》

Circ_0004676 exacerbates triple-negative breast cancer progression through regulation of the miR-377-3p/E2F6/PNO1 axis.

The significant roles of circular RNAs (circRNAs) in different cancers and diseases have been reported. We now focused on the possible role of a newly recognized circRNA, circ_0004674 in triple-negative breast cancer (TNBC), and the related downstream mechanism. The expression of circ_0004674 in TNBC tissues and cells was determined followed by analysis of the correlation between circ_0004674 and TNBC patients' prognosis. The interaction between circ_0004674, miR-377-3p, E2F6, and PNO1 was then identified using bioinformatics analysis combined with FISH, RIP, RNA pull-down, RT-qPCR, and Western blot analysis. Using gain-of-function and loss-of-function methods, we analyzed the effect of circ_0004674, miR-377-3p, E2F6, and PNO1 on TNBC in vivo and in vitro. Increased circ_0004674 and E2F6 but decreased miR-377-3p were observed in TNBC tissues and MDA-MB-231 TNBC cells, all of which findings were associated with poor prognosis in patients with TNBC. Silencing of circ_0004676 remarkably suppressed the proliferation, cell cycle progression, and migration of TNBC cells in vitro, as well as inhibiting tumorigenesis and metastasis in vivo. Additionally, circ_0004676 served as a sponge of miR-377-3p which bound to the transcription factor E2F6. In the presence of overexpression of circ_0004676, E2F6 expression and its target PNO1 expression were elevated, while miR-377-3p expression was decreased. Interestingly, overexpression of E2F6 could reverse the inhibitory effect on tumor growth caused by downregulation of circ_0004676. Our study highlighted the carcinogenic effect of circ_0004676 on TNBC through regulation of the miR-377-3p/E2F6/PNO1 axis. 1. Circ_0004674 is highly expressed in TNBC tissues and cells. 2. Circ_0004674 upregulates the expression of E2F6 by sponging miR-377-3p. 3. E2F6 upregulates PNO1 by binding to the PNO1 promoter. 4. Circ_0004674 favors TNBC progression by regulating the miR-377-3p/E2F6/PNO1 axis. 5. This study provides a new target for the treatment of TNBC.

Shao G ，Fan X ，Zhang P ，Liu X ，Huang L ，Ji S ... -  《-》

circ_0008797 attenuates non-small cell lung cancer proliferation, metastasis, and aerobic glycolysis by sponging miR-301a-3p/SOCS2.

This paper firstly reported the exact function of circ_0008797 on non-small cell lung cancer (NSCLC) progression. NSCLC tissues/matched normal tissues were harvested from 88 NSCLC patients. RNA fluorescence in situ hybridization experiment was applied to detect circ_0008797 localization in NSCLC cells. circ_0008797 effect on NSCLC cells proliferation, migration, invasion, glucolysis, and apoptosis was researched by cell counting kit-8 assay, 5-ethynyl-2'deoxyuridine assay, Transwell experiment, glycolysis assay, and TUNEL assay. Dual luciferase reporter gene assay, RNA pull-down assay and RNA immunoprecipitation assay were used to verify the binding relationship between two genes. In vivo tumorigenesis and lung metastasis was performed using nude mice. Quantitative reverse transcription-polymerase chain reaction, immunohistochemistry and western blot were applied for genes expression detection. Hematoxylin and eosin staining was performed on lung tissues. circ_0008797 was low expressed in NSCLC tissues and cell lines, associating with poor outcome (p <.05). circ_0008797 was mainly expressed in NSCLC cells cytoplasm. circ_0008797 inhibited proliferation, migration, invasion, and glycolysis, but enhanced apoptosis of NSCLC cells (p <.05). circ_0008797 attenuated malignant phenotype of NSCLC cells by sponging miR-301a-3p. circ_0008797 facilitated SOCS2 expression by sponging miR-301a-3p. SOCS2 knockdown partially reversed the inhibitory effect of miR-301a-3p inhibition on NSCLC cells malignant phenotype (p <.05). circ_0008797 attenuated NSCLC prolifearion and metastasis in vivo (p <.05). circ_0008797 attenuates NSCLC proliferation, metastasis and aerobic glycolysis by sponging miR-301a-3p/SOCS2.

Abuduwaili K ，Zhu X ，Shen Y ，Lu S ，Liu C ... -  《-》

Circular RNA ZNF609 functions as a competing endogenous RNA in regulating E2F transcription factor 6 through competitively binding to microRNA-197-3p to promote the progression of cervical cancer progression.

Gu Q ，Hou W ，Shi L ，Liu H ，Zhu Z ，Ye W ... -  《-》