Blocking circ_0010235 suppresses acquired paclitaxel resistance of non-small cell lung cancer by sponging miR-512-5p to modulate FAM83F expression.

The occurrence of paclitaxel (PTX) resistance in nonsmall cell lung cancer (NSCLC) is a major challenge for NSCLC treatment. Circular RNAs (circRNAs) have been reported to associate with cancer resistance, but the role of circ_0010235 in PTX resistance of NSCLC is unclear. The expression of circ_0010235 and microRNA-512-5p (miR-512-5p) were determined by quantitative real-time PCR. Cell counting kit-8 assay, transwell assay and flow cytometry were performed to measure the PTX resistance, proliferation, migration, invasion and apoptosis of cells. All proteins were assessed via western blot analysis. The combination between miR-512-5p and circ_0010235 or FAM83F was predicted by the online database and confirmed by a dual-luciferase reporter assay. Angiogenesis assay was used to detect the ability of cells to form blood vessels. Animal experiments were employed to confirm the effect of circ_0010235 on NSCLC tumor growth in vivo. Circ_0010235 and FAM83F were upregulated in PTX-resistant NSCLC tissues and cells. Circ_0010235 knockdown suppressed the resistance to PTX, proliferation, angiogenesis and migration/invasion in A549/PTX and H1299/PTX cells but promoted apoptosis rate. MiR-512-5p could be sponged by circ_0010235, and its overexpression had an inhibition effect on the PTX resistance of NSCLC cells. FAM83F was a target of miR-512-5p and circ_0010235 could modulate FAM83F expression by sponging miR-512-5p. In vivo experiments revealed that silenced circ_0010235 could improve the sensitivity of the tumor to PTX. Therefore, these findings advocated targeting the circ_0010235/miR-512-5p/FAM83F axis as a potential therapeutic option for patients with NSCLC who are resistant to PTX.

Li Y ，Ma Z ，Luo M ，Liang R ... -  《-》

Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non-small cell lung cancer via positively modulating KPNA4 by sponging miR-1298-5p.

Circ_0000376 could promote non-small cell lung cancer (NSCLC) progression; however, the role of circ_0000376 in paclitaxel (PTX) resistance of NSCLC is still unknown. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied for measuring circ_0000376, microRNA-1298-5p (miR-1298-5p), and karyopherin subunit alpha 4 (KPNA4) expression. The half inhibitory concentration (IC50) of PTX was assessed by cell counting kit-8 assay. 5-ethynyl-2'-deoxyuridine assay, wound healing assay, transwell assay, and flow cytometry were performed to measure the proliferation, migration, invasion, and apoptosis of cells. The regulatory mechanisms of circ_0000376, miR-1298-5p, and KPNA4 were validated by dual-luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. Xenograft assay was used for the functional analysis of circ_0000376 in vivo. Circ_0000376 and KPNA4 expressions were upregulated, while miR-1298-5p expression was downregulated in PTX-resistant tissues and cells. Circ_0000376 depletion promoted PTX sensitivity and apoptosis, while suppressing the proliferation, migration, and invasion of PTX-resistant NSCLC cells. Furthermore, circ_0000376 could modulate KPNA4 expression by sponging miR-1298-5p. Rescue experiments showed that miR-1298-5p inhibition reversed the circ_0000376 depletion-mediated anticancer effects and PTX sensitivity. Moreover, miR-1298-5p inhibited PTX resistance and tumorigenesis of PTX-resistant cells, which were abolished by KPNA4 overexpression. In addition, circ_0000376 knockdown suppressed tumor growth and enhanced PTX sensitivity in vivo. Circ_0000376 facilitated PTX resistance and tumorigenesis of NSCLC by miR-1298-5p/KPNA4 axis, suggesting an underlying therapeutic strategy for NSCLC.

Hu S ，Zhang Q ，Sun J ，Xue J ，Wang C ... -  《-》

Circ_0011292 Enhances Paclitaxel Resistance in Non-Small Cell Lung Cancer by Regulating miR-379-5p/TRIM65 Axis.

Guo C ，Wang H ，Jiang H ，Qiao L ，Wang X ... -  《-》

Circ_0000735 enhances the proliferation, metastasis and glycolysis of non-small cell lung cancer by regulating the miR-635/FAM83F axis.

Tai G ，Zhang M ，Liu F 《-》

Circ_0011292 knockdown mitigates progression and drug resistance in PTX-resistant non-small-cell lung cancer cells by regulating miR-433-3p/CHEK1 axis.

Non-small-cell lung cancer (NSCLC) is one of the most common malignant tumors on earth. Circular RNAs have been disclosed to be vital regulators in the chemoresistance and development of diverse cancers, including NSCLC. Here, we attempted to explore the function of circ_0011292 in paclitaxel (PTX)-resistant NSCLC cells. Quantitative real-time polymerase chain reaction or western blot was performed to detect the expression of circ_0011292, microRNA-433-3p (miR-433-3p), and checkpoint kinase 1 (CHEK1). Ribonuclease R (RNase R) assay was performed to assess the stability of circ_0011292. Cell Counting Kit-8 assay was conducted to evaluate the half maximal inhibitory concentration of PTX and cell viability. Cell proliferation was monitored by Edu incorporation and colony formation assays. Cell cycle and apoptosis were detected by flow cytometry. Transwell assay was implemented to assess cell migration and invasion. Western blot assay was utilized to determine the protein levels. Dual-luciferase reporter assay was carried out to verify the targeted interaction between miR-433-3p and circ_0011292 or CHEK1. Xenograft tumor model was constructed for determining the effect of circ_0011292 in NSCLC growth in vivo. Circ_0011292 was upregulated in PTX-resistant NSCLC tissues and cells. Circ_0011292 or CHEK1 knockdown enhanced PTX sensitivity and cell apoptosis, and repressed cell proliferation, migration, and invasion in PTX-resistant NSCLC cells. Mechanistically, circ_0011292 was a sponge of miR-433-3p and miR-433-3p directly targeted CHEK1. Meanwhile, silencing miR-433-3p or overexpressing CHEK1 respectively abrogated the impacts of circ_0011292 deletion or miR-433-3p introduction on PTX resistance and cell progression in PTX-resistant NSCLC cells in vitro. Moreover, circ_0011292 could positively modulate CHEK1 expression through sponging miR-433-3p. In addition, circ_0011292 knockdown retarded tumor growth of NSCLC in vivo. Circ_0011292 could accelerate PTX resistance and cell malignant progression of NSCLC cells partially through the regulation of circ_0011292/miR-433-3p/CHEK1 axis.

Jin M ，Zhang F ，Li Q ，Xu R ，Liu Y ，Zhang Y ... -  《-》