Hsa_circ_0092887 targeting miR-490-5p/UBE2T promotes paclitaxel resistance in non-small cell lung cancer.

Chemoresistance is a major contributing factor to cancer treatment failure. Emerging research reveals that circular RNA (circRNA) dysregulation is implicated in chemoresistance. Our current study aimed to investigate the involvement of hsa_circ_0092887 in paclitaxel (PTX) resistance in non-small cell lung cancer (NSCLC). RT-qPCR as well as western blotting were used for the analysis of hsa_circ_0092887, miR-490-5p and UBE2T expression in PTX-resistant NSCLC tumor tissues and cells. CCK-8 assay was done to determine the IC50 value of PTX. CCK-8 assay, wound healing assay, analysis of apoptosis related proteins (Bax and Bcl-2), and xenograft mouse models were utilized to investigate the role of hsa_circ_0092887 in PTX-resistance in NSCLC. The binding sites of miR-490-5p to hsa_circ_0092887 or UBE2T were predicted by bioinformatics tools and were verified by RIP and dual-luciferase assays. Expression of hsa_Circ_0092887 was upregulated in NSCLC tumor samples/cell lines, and its expression was also higher in PTX-resistant tumor samples/cell lines when compared with their respective controls. Silencing of hsa_circ_0092887 in PTX-treated NSCLC cells inhibited cell proliferation and migration, induced apoptosis, and suppressed tumor growth in xenograft mouse models in vivo. MiR-490-5p was a direct target of hsa_circ_0092887, and UBE2T was a functional downstream target of hsa_circ_0092887/miR-490-5p axis. Hsa_circ_0092887 depletion-induced anti-cancer effects in PTX-treated NSCLC cells were reversed by miR-490-5p inhibitor. Furthermore, inhibition of miR-490-5p strengthened UBE2T expression, thereby attenuating the anti-cancer effects caused by UBE2T knockdown. Hsa_circ_0092887 depletion alleviated PTX-resistance in NSCLC cells via modulating the miR-490-5p/UBE2T axis, and the targeted management of hsa_circ_0092887-mediated signaling axis might contribute to PTX-resistance intervention in NSCLC.

Wang L ，Zhang Z ，Tian H 《-》

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 ... -  《-》

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 ... -  《-》

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 ... -  《-》

Blocking hsa_circ_0074027 suppressed non-small cell lung cancer chemoresistance via the miR-379-5p/IGF1 axis.

Zheng S ，Wang C ，Yan H ，Du Y ... -  《-》