Circ_0072088 knockdown contributes to cisplatin sensitivity and inhibits tumor progression by miR-944/LASP1 axis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is an aggressive tumor that accounts for a large proportion of cancer-related deaths. Cisplatin (CDDP) has been utilized to treat NSCLC. However, the efficacy of CDDP is usually restrained owing to the development of drug resistance. This study aims to reveal the molecular mechanism of the resistance of NSCLC cells to CDDP. The expression levels of circRNA_0072088 (circ_0072088), microRNA-944 (miR-944), and LIM and SH3 protein 1 (LASP1) were measured by quantitative real-time PCR (qRT-PCR) in CDDP-resistant NSCLC tissues and cells. Protein expression was determined by Western blotting in CDDP-resistant NSCLC tissues and cells. The functional effects of circ_0072088, miR-944, and LASP1 on CDDP sensitivity and NSCLC progression were revealed by Cell Counting Kit-8 (CCK-8), flow cytometry, cell colony formation, wound healing, and transwell invasion assays. The binding relationship between miR-944 and circ_0072088 or LASP1 was identified by a dual-luciferase reporter and RNA immunoprecipitation assay. The effects of circ_0072088 knockdown on tumor growth in vivo were analyzed by an in vivo tumor formation assay. Circ_0072088 and LASP1 expression were significantly upregulated, while miR-944 expression was downregulated in CDDP-resistant NSCLC tissues and cells as compared with control groups. Circ_0072088 expression was significantly associated with tumor-node-metastasis stage and tumor size. Functionally, circ_0072088 knockdown improved CDDP sensitivity and repressed NSCLC cell malignancy, whereas miR-944 inhibitor hindered these effects. Mechanistically, circ_0072088 functioned as a sponge for miR-944 and miR-944 targeted LASP1. Circ_0072088 knockdown improved the sensitivity of tumor to CDDP in vivo. Circ_0072088 silencing improved CDDP sensitivity and inhibited NSCLC progression by downregulating LASP1 expression through sponging miR-944. These data provide novel insight into the resistance of NSCLC to CDDP.

Zhang L ，Wu Y ，Hou C ，Li F ... -  《-》

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 ... -  《-》

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 ... -  《-》

Serum Exosomes-Based Biomarker circ_0008928 Regulates Cisplatin Sensitivity, Tumor Progression, and Glycolysis Metabolism by miR-488/HK2 Axis in Cisplatin-Resistant Nonsmall Cell Lung Carcinoma.

Shi Q ，Ji T ，Ma Z ，Tan Q ，Liang J ... -  《-》

Circular RNA circ_0006948 Promotes Esophageal Squamous Cell Carcinoma Progression by Regulating microRNA-3612/LASP1 Axis.

Esophageal squamous cell carcinoma (ESCC) is the most prevalent malignancy worldwide. Circular RNAs (circRNAs) circ_0006948 is reported to be upregulated in ESCC cells. This study is designed to explore the role and mechanism of circ_0006948 in ESCC progression. Circ_0006948, linear FNDC3B, microRNA-3612 (miR-3612), and LIM and SH3 protein 1 (LASP1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, colony number, migration, invasion, and apoptosis were examined by Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays, severally. Glucose consumption, lactate production, and ATP level were measured by the corresponding kits. Protein levels of hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), and LASP1 were assessed by western blot assay. The cytoplasmic localization of circ_0006948 was identified by the subcellular fractionation assay. The binding relationship between miR-3612 and circ_0006948 or LASP1 was predicted by starBase or TargetScan and then verified by a dual-luciferase reporter assay. The biological role of circ_0006948 on ESCC tumor growth was examined by the xenograft tumor model in vivo. Circ_0006948 and LASP1 were increased, and miR-3612 was decreased in ESCC tissues and cells. Furthermore, circ_0006948 knockdown could suppress cell viability, colony number, migration, invasion, glycolysis, and boost apoptosis in ESCC cells. Mechanically, circ_0006948 could act as a sponge of miR-3612 to regulate LASP1 expression. In addition, circ_0006948 silencing inhibited ESCC tumor growth in vivo. Circ_0006948 boosted ESCC progression partly by regulating the miR-3612/LASP1 axis, providing an underlying therapeutic target for the ESCC treatment.

Tang R ，Zhou Q ，Xu Q ，Lu L ，Zhou Y ... -  《-》