Circ-UBR1 facilitates proliferation, metastasis, and inhibits apoptosis in breast cancer by regulating the miR-1299/CCND1 axis.

Circular RNA (circRNA) is abnormally expressed in cancers and has been linked to cancer progression, including breast cancer (BC). However, the role and mechanism of circ-UBR1 in BC progression remains to be further studied. Quantitative real-time PCR (qRT-PCR) was conducted to analyze the expression of circ-UBR1, miR-1299 and Cyclin D1 (CCND1). Cell counting kit 8 (CCK8) assay was used to measure cell viability. Cell apoptosis and cell cycle distribution were analyzed by flow cytometry. Then, the migration and invasion of cells were determined by transwell assay. Moreover, BC tumor xenograft model was built to evaluate the function of circ-UBR1 silencing on BC tumor volume and weight. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to illuminate the interaction between miR-1299 and circ-UBR1 or CCND1. In addition, relative CCND1 protein expression was assessed using western blot (WB) analysis. Our results revealed that circ-UBR1 was upregulated in BC, and its silencing could inhibit BC cell proliferation, metastasis, and promote apoptosis in vitro, as well as restrain BC tumor growth in vivo. Meanwhile, we found that circ-UBR1 could sponge miR-1299, and miR-1299 inhibitor could reverse the effect of circ-UBR1 knockdown on BC cell progression. Furthermore, CCND1 was a target of miR-1299, and CCND1 overexpression could reverse the effect of miR-1299 mimic on BC cell progression. Also, the downregulation of circ-UBR1 could inhibit CCND1 expression, while this effect could be inverted by miR-1299 inhibitor. Our data indicated that circ-UBR1 might play a pro-cancer role in BC progression by regulating the miR-1299/CCND1 axis.

Zhang L ，Sun D ，Zhang J ，Tian Y ... -  《-》

Circ-RNF111 contributes to paclitaxel resistance in breast cancer by elevating E2F3 expression via miR-140-5p.

Circular RNAs (circRNAs) have been demonstrated to act as key regulators in the chemoresistance of human cancers, including breast cancer (BC). Here, we aimed to explore the role of circ-RNF111 in paclitaxel (PTX) resistance of BC. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ-RNF111, microRNA-140-5p (miR-140-5p) and E2F transcription factor 3 (E2F3) mRNA. The half maximal inhibitory concentration (IC50 ) of PTX, cell viability, colony formation and cell invasion were assessed by cell counting kit-8 (CCK-8) assay, colony formation assay and transwell assay, respectively. Glucose consumption and lactate production were determined by specific kits. A murine xenograft model was established to investigate the role of circ-RNF111 in PTX resistance of BC in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the relationship between miR-140-5p and circ-RNF111 or E2F3. Western blot assay was conducted to examine the protein level of E2F3. Circ-RNF111 was upregulated in PTX-resistant BC tissues and cells. Circ-RNF111 knockdown restrained IC50 of PTX, cell viability, colony numbers, cell invasion and glycolysis in PTX-resistant BC cells in vitro and enhanced PTX sensitivity in vivo. MiR-140-5p was a target of circ-RNF111 and miR-140-5p expression was negatively correlated with circ-RNF111 expression in BC tissues. The effect of circ-RNF111 knockdown on PTX resistance was rescued by miR-140-5p deletion. Additionally, miR-140-5p could interact with E2F3 and negatively regulate E2F3 expression. Moreover, miR-140-5p suppressed IC50 of PTX, cell viability, colony numbers, cell invasion and glycolysis by targeting E2F3. Circ-RNF111 improved PTX resistance of BC by upregulating E2F3 via sponging miR-140-5p.

Zang H ，Li Y ，Zhang X ，Huang G ... -  《-》

Circular RNA 0007255 regulates the progression of breast cancer through miR-335-5p/SIX2 axis.

Breast cancer (BC) is a common cancer in women worldwide. Emerging evidence has indicated that circular RNA hsa-circ_0007255 (circ_0007255) is a prognostic mediator in BC progression. However, the functional role of circ_0007255 needs to be determined. The expression of circ_0007255, microRNA (miR)-335-5p, and SIX Homeobox 2 (SIX2) was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Actinomycin D and RNase R treatment was performed to analyze the stability of circ_0007255. Additionally, Seahorse extracellular flux, colony formation and transwell analyses were carried out to detect oxygen consumption ratio (OCR), colony formation and cell mobility, respectively. The interaction between miR-335-5p and circ_0007255 or SIX2 was confirmed via dual-luciferase reporter assay. A xenograft tumor model was established to explore the role of circ_0007255 in vivo. Circ_0007255 and SIX2 were overexpressed, but miR-335-5p was diminished in BC tissues and cells. Circ_0007255 absence inhibited oxygen consumption, colony formation, cell migration and invasion, and these effects were particularly abrogated via miR-335-5p upregulation in BC cells. Moreover, SIX2 deficiency eliminated the promotion effects of miR-335-5p inhibitor on oxygen consumption, colony formation, and cell mobility in BC cells. Importantly, circ_0007255 inhibited tumor growth in vivo. Mechanically, circ_0007255 was a sponge of miR-335-5p to regulate SIX2 expression in BC progression. Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR-335-5p/SIX2 axis, and might be a promising biomarker for BC treatment. Significant findings of the study: Levels of circ_0007255 and SIX2 were upregulated, but miR-335-5p was diminished in BC tissues and cells. Circ_0007255 was an oncogene in BC development and exerted its function via miR-335-5p/SIX2 axis in BC. Tumor growth was reduced by circ_0007255 absence. Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR-335-5p/SIX2 axis, and might be a promising biomarker for BC treatment.

Jia Q ，Ye L ，Xu S ，Xiao H ，Xu S ，Shi Z ，Li J ，Chen Z ... -  《-》

Circ_0023028 contributes to the progression of laryngeal squamous cell carcinoma by upregulating LASP1 through miR-486-3p.

Zheng Y ，Duan L ，Yang Y ，Luo D ，Yan B ... -  《-》

Circular RNA circ_0007142 regulates cell proliferation, apoptosis, migration and invasion via miR-455-5p/SGK1 axis in colorectal cancer.

Colorectal cancer (CRC) is a frequently diagnosed cancer worldwide. Accumulating researches suggested that circular RNA 0007142 (circ_0007142) contributed to the progression and initiation of CRC. However, the molecular mechanism of circ_0007142 in CRC needs further research. Levels of circ_0007142, microRNA-455-5p (miR-455-5p), and serum- and glucocorticoid-induced protein kinase 1 (SGK1) were identified by quantitative real-time PCR. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide assay. Flow cytometry assay was used to detect cell apoptosis in SW480 and HCT116 cells. The relative proteins expression was detected by western blot. Cell migration and invasion were evaluated using transwell assay. Moreover, dual-luciferase reporter and RNA immunoprecipitation assays were conducted to determine the relationship between miR-455-5p and circ_0007142 or SGK1. Finally, xenograft tumor model was established to confirm the effect of circ_0007142 on CRC progression in vivo. Circ_0007142 and SGK1 levels were clearly increased, while miR-455-5p level was reduced in CRC tissues and cell lines. Circ_0007142 silencing promoted cell apoptosis and inhibited cell proliferation, migration and invasion, while these effects of circ_0007142 were partially abolished by miR-455-5p inhibitor in CRC cells. Circ_0007142 could sponge miR-455-5p to regulate SGK1 expression. Moreover, the effects of miR-455-5p on cell proliferation, apoptosis, migration and invasion could be partially reversed by SGK1 overexpression. Besides, circ_0007142 knockdown also suppressed the progression of CRC in vivo. Collectively, Circ_0007142/miR-455-5p/SGK1 axis regulated cell proliferation, apoptosis, migration and invasion of CRC cells, providing a probable therapy target for CRC.

Wen T ，Wu H ，Zhang L ，Li K ，Xiao X ，Zhang L ，Zhang Y ... -  《-》