Cisplatin resistance and malignant behaviors of lung cancer cells are promoted by circ_0002360 via targeting miR-6751-3p to regulate the expression of ZNF300.

Circular RNAs (circRNAs) are key regulators in oncogenesis and chemoresistance of human cancers. Herein, we focused on the roles of circ_0002360 in regulating lung cancer progression and cisplatin (DDP) resistance. The detection of circ_0002360, microRNA-6751-3p (miR-6751-3p) and zinc finger protein 300 (ZNF300) was conducted via reverse transcription-quantitative polymerase chain reaction assay. Cell sensitivity was determined using cell counting kit-8 assay. Proliferation detection was performed by colony formation assay and EdU assay. The migrated cells were examined via transwell assay. Cell apoptosis analysis was carried out through flow cytometry and caspase 3 activity assay. Western blot was used to examine the protein levels. Target interaction was confirmed through dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ_0002360 function in vivo was performed via xenograft tumor assay. Circ_0002360 was overexpressed in DDP-resistant lung cancer tissues and cells. Silencing circ_0002360 inhibited DDP resistance, proliferation and migration but enhanced apoptosis of DDP-resistant cells. Circ_0002360 could elevate ZNF300 expression. DDP resistance and lung cancer progression were also impeded by ZNF300 downregulation. ZNF300 overexpression reversed the function of circ_0002360 knockdown in DDP-resistant lung cancer cells. The regulation of circ_0002360 for ZNF300 was achieved by sponging miR-6751-3p. Circ_0002360 promoted DDP resistance in xenograft mice through mediating the miR-6751-3p/ZNF300 axis. Circ_0002360 targeted miR-6751-3p to regulate ZNF300 level, thus elevating DDP resistance and promoting the malignant progression of lung cancer cells.

Ding L ，Li L ，Tang Z 《-》

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_0020123 enhances the cisplatin resistance in non-small cell lung cancer cells partly by sponging miR-140-3p to regulate homeobox B5 (HOXB5).

Wei D ，Zeng J ，Rong F ，Xu Y ，Wei R ，Zou C ... -  《-》

circ_0007385 served as competing endogenous RNA for miR-519d-3p to suppress malignant behaviors and cisplatin resistance of non-small cell lung cancer cells.

Circular RNAs (circRNAs) have been closely implicated in competing endogenous RNA (ceRNA) network among human cancers including non-small cell lung cancer (NSCLC). However, the role of most circRNAs in NSCLC remains to be determined. Here, we aimed to investigate the role of hsa_circ_0007385 (circ_0007385) in NSCLC cells. Expression of hsa_circ_0007385 (circ_0007385), miRNA (miR)-519d-5p and high-mobility group box 1 (HMGB1) was measured by real-time quantitative PCR and western blotting. Functional experiments were evaluated by cell counting kit (CCK)-8, flow cytometry, fluorescein active caspase-3 staining kit, transwell assays, western blotting, and xenograft experiment. The relationship among circ_0007385,miR-519d-5p and HMGB1 was testified by dual-luciferase reporter assay. Kaplan-Meiersurvival curve identified overall survival in NSCLC patients. circ_0007385 expression was higher in NSCLC tissues and cell lines, and was associated with poor overall survival. Silencing circ_0007385 could suppress cell proliferation, migration and invasion in A549 and H1975 cells, as well as cisplatin (DDP) resistance. Moreover, circ_0007385 silence retarded tumor growth of A549 cells in vivo. Molecularly, there was a direct interaction between miR-519d-3p and either circ_0007385 or HMGB1; expression of miR-519d-3p was downregulated in NSCLC tumors in a circ_0007385-correlated manner, and circ_0007385 could indirectly regulate HMGB1 via miR-519d-3p. Functionally, both inhibiting miR-519d-3p and restoring HMGB1 could overturn the suppressive effect of circ_0007385 knockdown on cell proliferation, migration, invasion, and DDP resistance. Collectively, circ_0007385 deletion could function anti-tumor role in NSCLC by suppressing malignant behaviors and DDP resistance in vitro and in vivo via circ_0007385/miR-519d-3p/HMGB1 axis. These outcomes might enhance our understanding of the molecular mechanisms underlying the malignant progression of NSCLC. SIGNIFICANT FINDINGS OF THE STUDY: circ_0007385 was upregulated in NSCLC tissues and cells, and was associated with poor overall survival. Silenced circ_0007385 suppressed NSCLC cell proliferation, migration, invasion, and DDP resistance in vitro, and tumor growth in vivo. circ_0007385 was upregulated in NSCLC tissues and cells, and was associated with poor overall survival. miR-519d-3p could directly interact with circ_0007385 and HMGB1 in NSCLC cells. A promising circ_0007385/miR-519d-3p/HMGB1 regulatory pathway was determined in NSCLC cells.

Ye Y ，Zhao L ，Li Q ，Xi C ，Li Y ，Li Z ... -  《-》

Hsa_circ_0007142 contributes to cisplatin resistance in esophageal squamous cell carcinoma via miR-494-3p/LASP1 axis.

Chemoresistance is one of the major obstacles for tumor treatment. Circular RNAs (circRNAs) have been confirmed to play vital roles in chemoresistance of cancer, including esophageal squamous cell carcinoma (ESCC). We investigated the roles and mechanisms of circ_0007142 in cisplatin (DDP) resistance of ESCC. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the levels of circ_0007142, DOCK1 mRNA, microRNA-494-3p (miR-494-3p) and LIM And SH3 Protein 1 (LASP1) mRNA. RNase R assay was conducted to analyze the characteristic of circ_0007142. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate IC50 of DDP. Flow cytometry analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay and transwell assay were carried out to examine cell apoptosis, proliferation and invasion, respectively. Dual-luciferase reporter assay was employed to verify the association between miR-494-3p and circ_0007142 or LASP1. Murine xenograft assay was conducted to investigate the role of circ_0007142 in DDP resistant in vivo. The protein level of LASP1 in tumors was measured by Immunohistochemistry (IHC) analysis. Circ_0007142 was upregulated in DDP-resistant ESCC tissues and cells. Circ_0007142 knockdown improved DDP sensitivity, induced cell apoptosis and hampered cell proliferation and invasion in DDP-resistant ESCC cells. Circ_0007142 functioned as the sponge for miR-494-3p and miR-494-3p inhibition reversed the impacts of circ_0007142 knockdown on DDP resistance, cell apoptosis, proliferation, and invasion. LASP1 was a target of miR-494-3p, and the effects on DDP resistance, cell apoptosis, growth, and invasion mediated by LASP1 downregulation were rescued by miR-494-3p inhibition. Moreover, circ_0007142 knockdown enhanced DDP sensitivity in vivo. Circ_0007142 improved DDP resistance of ESCC by upregulating LASP1 via sponging miR-494-3p.

Chang N ，Ge N ，Zhao Y ，Yang L ，Qin W ，Cui Y ... -  《-》