Circ_0026123 promotes cisplatin resistance and progression of ovarian cancer by upregulating RAB1A through sequestering miR-543.

Circular RNAs can act as critical regulators in the tumorigenesis and chemoresistance of ovarian cancer (OC). Herein, this work aimed to probe the function and mechanism of circ_0026123 in the cisplatin (DDP) resistance and progression of OC and its potential value in the clinic. The quantitative real-time PCR and western blotting were used to detect the levels of RNAs and proteins. In vitro experiments were conducted using CCK-8, EdU, transwell, tube formation assays and flow cytometry. Mouse subcutaneous xenograft model was used for in vivo experiments. The interaction between circ_0026123 or RAB1A (Ras-related protein Rab-1A) and miR-543 was confirmed using dual-luciferase reporter and RNA immunoprecipitation assays. Circ_0026123 expression was higher in DDP-resistant OC tissues and cells. Silencing of circ_0026123 dramatically boosted the sensitivity of DDP-resistant OC cells to DDP, as well as inhibited cell growth, angiogenesis, invasion and migration abilities in vitro. Circ_0026123 functionally targeted miR-543, and knockdown of miR-543 reversed the impacts of circ_0026123 deficiency on DDP sensitivity and the malignant behaviors of DDP-resistant OC cells. RAB1A was a target of miR-543, RAB1A overexpression attenuated the inhibitory functions of miR-543 on DDP resistance and the malignant phenotypes of DDP-resistant OC cells. Preclinically, lentivirus-mediated circ_0026123 downregulation also suppressed OC growth and enhanced DDP cytotoxicity in vivo. Our study demonstrated that circ_0026123 acted as a sponge for miR-543 to elevate RAB1A expression, thus promoting cisplatin resistance and tumorigenesis in ovarian cancer.

Wei L ，He W ，Zhao H ，Zhao P ... -  《-》

Circ_0061140 Contributes to the Malignant Progression in Ovarian Cancer Cells by Mediating the RAB1A Level Through Sponging miR-361-5p.

Ovarian cancer (OC) progression is related to many functional molecules, including circular RNAs (circRNAs). Hsa_circ_0061140 (circ_0061140) promoted cell growth and metastasis in OC. The aim of this study was to explore a specific functional mechanism of circ_0061140. Reverse transcription-quantitative polymerase chain reaction was performed for expression analysis of circ_0061140, microRNA-361-5p (miR-361-5p), and Ras-like protein in rat brain 1A (RAB1A). Cell proliferation was determined using Cell Counting Kit-8 assay, EdU assay, and colony formation assay. The migration and invasion were assessed through transwell assay. Tube formation assay was used for angiogenesis analysis. Cell apoptosis was evaluated using flow cytometry. The protein levels of epithelial-to-mesenchymal transition (EMT) markers and RAB1A were detected via western blot. Target analysis was performed by dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo research was conducted using xenograft model. The circ_0061140 level was upregulated in OC samples and cells. Downregulation of circ_0061140 impeded proliferation, migration, invasion, EMT, and angiogenesis of OC cells. Circ_0061140 directly interacted with miR-361-5p to act as a miRNA sponge. The miR-361-5p inhibition reversed the si-circ_0061140-induced anti-tumor function in OC cells. RAB1A was a downstream target of miR-361-5p, and miR-361-5p served as a tumor repressor in OC via inhibiting the level of RAB1A. Circ_0061140 could increase the RAB1A expression by sponging miR-361-5p in OC cells. Circ_0061140 also facilitated tumorigenesis in vivo through targeting the miR-361-5p/RAB1A axis. All results demonstrated that circ_0061140 promoted OC development by inhibiting miR-361-5p to upregulate the expression of RAB1A.

Zhang Y ，Di Q ，Chen J ，Chang M ，Ma Y ，Yu J ... -  《-》

Circ_0007841 knockdown confers cisplatin sensitivity to ovarian cancer cells by down-regulation of NFIB expression in a miR-532-5p-dependent manner.

Gao Y ，Huang Y 《-》

Knockdown of circ-PIP5K1A overcomes resistance to cisplatin in ovarian cancer by miR-942-5p/NFIB axis.

Cisplatin (DDP)-based chemotherapy is the main chemotherapeutic agent for ovarian cancer (OC) treatment. Circular RNA PIP5K1A (circ-PIP5K1A) was found to promote OC tumorigenesis. However, whether circ-PIP5K1A was involved in DDP resistance in OC remains unclear. Levels of circ-PIP5K1A, microRNA (miR)-942-5p, and nuclear factor I B (NFIB) were detected using quantitative real-time PCR and Western blot assays. In-vitro experiments were conducted by using cell counting kit-8, cell colony formation, 5-ethynyl-2'-deoxyuridine, flow cytometry, and transwell assays, respectively. In-vivo assay was performed using murine xenograft model. The binding interaction between miR-942-5p and circ-PIP5K1A or NFIB was confirmed using dual-luciferase reporter assay. Exosomes were obtained from culture media by the use of commercial kits and qualified by transmission electron microscopy and Western blot. Circ-PIP5K1A was highly expressed in DDP-resistant OC tissues and cells. Circ-PIP5K1A knockdown could constrain the proliferation, migration, and invasion, as well as increase apoptosis and sensitivity to DDP in DDP-resistant OC cells. Mechanistically, circ-PIP5K1A acted as a sponge for miR-942-5p to positively regulate NFIB expression. Moreover, rescue experiments demonstrated that the anticancer and DDP sensitization effects caused by circ-PIP5K1A silencing in DDP-resistant OC cells were achieved through the miR-942-5p/NFIB axis. Importantly, circ-PIP5K1A silencing enhanced DDP efficacy and impeded tumor growth in OC in vivo . Additionally, we also found that circ-PIP5K1A was packaged into exosomes and could be internalized by surrounding cells. Circ-PIP5K1A knockdown reduced the resistance to DDP in OC via regulating miR-942-5p/NFIB axis. Besides that, circ-PIP5K1A was packaged into exosomes and exosomal circ-SKA3 could mediate intercellular communication between OC cells. These findings provided a promising therapeutic target for OC.

Sheng H ，Wang X 《-》

Circ_0010235 confers cisplatin resistance in lung cancer by upregulating E2F7 through absorbing miR-379-5p.

Cisplatin (DDP) treatment is one of the most predominant chemotherapeutic strategies for lung cancer patients. Circular RNAs (circRNAs) have been revealed to participate in the chemoresistance in lung cancer. Hence, the role and mechanism of circ_0010235 in cisplatin resistance in lung cancer was investigated. Expression levels of circ_0010235, microRNA (miR)-379-5p and E2F transcription factor 7 (E2F7) were analyzed using quantitative reverse transcription PCR (qRT-PCR) and western blot. Cell DDP sensitivity, proliferation, apoptosis, invasion, and migration were detected by cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine (EDU) assay, flow cytometry and western blot, respectively. The binding interaction was verified using dual-luciferase reporter assay. A murine xenograft model was established to investigate effects in vivo. Circ_0010235 was highly expressed in DDP-resistant lung cancer tissues and cells. Knockdown of circ_0010235 elevated DDP sensitivity, constrained proliferation, invasion and migration as well as fostered apoptosis in DDP-resistant lung cancer cells. Moreover, circ_0010235 silencing boosted DDP sensitivity and impeded tumor growth in lung cancer in vivo. Mechanistically, circ_0010235 acted as a sponge for miR-379-5p to elevate the expression of its target E2F7. Rescue experiments showed that miR-379-5p inhibition attenuated circ_0010235 knockdown-evoked reduction on DDP resistance of DDP-resistant cancer cells. In addition, miR-379-5p re-expression elevated DDP sensitivity and suppressed the malignant phenotype of DDP-resistant lung cancer cells through miR-379-5p. Circ_0010235 knockdown reduced DDP resistance and tumor growth via miR-379-5p/ E2F7 axis in lung cancer, suggesting an effective therapeutic target for lung cancer patients.

Wang L ，Wang D ，Xu Z ，Qiu Y ，Chen G ，Tan F ... -  《-》