Circ_0001786 facilitates gefitinib resistance and malignant progression in non-small cell lung cancer via miR-34b-5p/SRSF1.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a widespread cancer and gefitinib is a primary therapy for NSCLC patients. Nevertheless, the underlying mechanisms for the progression of acquired drug resistance have not been clarified. The aim of this study was to investigate the role of circular RNA (circ_0001786) in gefitinib-resistant NSCLC. METHODS: Firstly, the expression of circ_0001786, miR-34b-5p and SRSF1 were assayed using qRT-PCR. Subsequently, CCK-8 test was utilized to measure the semi-inhibitory concentration (IC50) of cellular gefitinib. Apoptosis was identified by flow cytometry. At last, dual luciferase assay was applied to prove the binding association between miR-34b-5p, circ_0001786 or SRSF1. RESULTS: Our research disclosed that circ_0001786 was heightened in gefitinib-resistant NSCLC cells and tissues. Knockdown of circ_0001786 restrained IC50 values of gefitinib, attenuated the clonogenic ability and facilitated apoptosis in HCC827-GR and PC9-GR. In addition, circ_0001786 was a molecular sponge for miR-34b-5p. Silencing miR-34b-5p rescued the inhibitory impact of circ_0001786 knockdown on IC50 and cell cloning ability. Moreover, miR-34b-5p directly targeted SRSF1. Importantly, circ_0001786 enhanced gefitinib tolerance and malignant development in NSCLC through miR-34b-5p/SRSF1 pathway. CONCLUSION: This research revealed a novel mechanism by which circ_0001786 enhanced NSCLC resistance to gefitinib by sponging miR-34b-5p and upregulating SRSF1. circ_0001786 was a potential target for improving the treatment of gefitinib-resistant NSCLC patients.

MicroRNA-140-5p suppresses cell proliferation and invasion in gastric cancer by targeting WNT1 in the WNT/ß-catenin signaling pathway.

MicroRNAs have been suggested as potential regulators in gastric cancer (GC) development through affecting the expression of their target genes. Previous studies have demonstrated that miR-140-5p is downregulated in GC. However, the underlying functional role of miR-140-5p in GC remains largely unknown. The present study revealed that miR-140-5p expression was significantly decreased in 60 GC tissues, compared with corresponding adjacent non-tumor tissues. A lower miR-140-5p expression was significantly associated with lymph node metastasis and an advanced Tumor-Node-Metastasis stage in patients with GC. Furthermore, patients with a lower miR-140-5p expression exhibited shorter disease-free survival and overall survival times. Gain- and loss-of-function assays revealed that increased miR-140-5p expression significantly inhibited GC cell proliferation and invasion ability, as well as the Wnt/ß-catenin signaling pathway by decreasing WNT1 and ß-catenin expression. However, decreasing miR-140-5p expression had the opposite effects. Bioinformatics methods and dual-luciferase reporter assays revealed that WNT1 was a direct target of miR-140-5p. miR-140-5p suppressed cell proliferation and invasion by regulating WNT1 expression. Therefore, the results of the present study demonstrated that miR-140-5p may serve as a potential prognostic marker and therapeutic target in patients with GC.