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_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 《-》

Circ_PIP5K1A regulates cisplatin resistance and malignant progression in non-small cell lung cancer cells and xenograft murine model via depending on miR-493-5p/ROCK1 axis.

Chemoresistance limits the therapeutic effect of cisplatin (DDP) on non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) function as important regulators in chemoresistance. This study aimed to explore the regulation of circRNA Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Alpha (circ_PIP5K1A) in DDP resistance. The expression analysis of circ_PIP5K1A, micoRNA-493-5p (miR-493-5p) and Rho Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1) was conducted through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell sensitivity was determined using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell proliferation and cell viability were evaluated by colony formation assay and MTT assay, respectively. Cell cycle and apoptosis detection was performed via flow cytometry. Cell motility was examined by transwell migration or invasion assay. Dual-luciferase reporter assay was applied to confirm the target binding. ROCK1 protein level was assayed via Western blot. In vivo assay was carried out using xenograft model in mice. Circ_PIP5K1A level was abnormally increased in DDP-resistant NSCLC tissues and cells. Silencing circ_PIP5K1A reduced DDP resistance, proliferation, cell cycle progression and cell motility in DDP-resistant NSCLC cells. Circ_PIP5K1A directly interacted with miR-493-5p in NSCLC cells. The function of circ_PIP5K1A was dependent on the negative regulation of miR-493-5p. MiR-493-5p directly targeted ROCK1 and circ_PIP5K1A regulated the ROCK1 level via acting as a sponge of miR-493-5p. Overexpression of miR-493-5p inhibited chemoresistance and cancer progression by downregulating ROCK1 expression in DDP-resistant NSCLC cells. Circ_PIP5K1A regulated DDP sensitivity in vivo via the miR-493-5p/ROCK1 axis. These findings suggested that circ_PIP5K1A upregulated the ROCK1 expression to promote DDP resistance and cancer progression in NSCLC by sponging miR-493-5p.

Feng N ，Guo Z ，Wu X ，Tian Y ，Li Y ，Geng Y ，Yu Y ... -  《RESPIRATORY RESEARCH》

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 ... -  《-》

Exosomal circ_PIP5K1A regulates the progression of non-small cell lung cancer and cisplatin sensitivity by miR-101/ABCC1 axis.

Shao N ，Song L ，Sun X 《-》