CircPI4KA Overexpression Enhances Carcinogenesis and Glycolysis Metabolism in Papillary Thyroid Carcinoma by Causing the miR-1287-5p-Mediated NRP2 Expression Elevation.

Circular RNAs (circRNAs) are implicated in regulating the pathogenesis of papillary thyroid carcinoma (PTC). Herein, we aimed to investigate how circRNA phosphatidylinositol 4-kinase IIIα (circPI4KA, hsa_circ_0062389) functioned as an oncogene in PTC. CircPI4KA, microRNA-1287-5p (miR-1287-5p) and Neuropilin-2 (NRP2) level detection were completed by reverse transcription-quantitative polymerase chain reaction assay. Cell proliferation was assessed through Cell Counting Kit-8 assay, colony formation assay, and EdU assay. Transwell assay was used for detecting migration and invasion abilities. Cell migration was also determined by wound healing assay. Cell apoptosis was assessed using flow cytometry assay. The protein examination was performed using western blot. Glycolysis was evaluated via commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted for target analysis. The role of circPI4KA in vivo was explored and analyzed via tumor xenograft assay. CircPI4KA was significantly upregulated in PTC tissues and cells. Knockdown of circPI4KA suppressed proliferation, migration, invasion, glycolysis, and induced apoptosis of PTC cells. CircPI4KA interacted with miR-1287-5p in PTC cells. The antitumor function of circPI4KA downregulation was reversed by inhibition of miR-1287-5p. The miR-1287-5p directly targeted NRP2, and circPI4KA elevated the NRP2 expression by sponging miR-1287-5p. PTC progression was impeded by miR-1287-5p via targeting NRP2. Silencing circPI4KA inhibited tumor growth in vivo through the miR-1287-5p/NRP2 axis. The collective results revealed that circPI4KA induced the upregulation of NRP2 via sponging miR-1287-5p, thus acting as a carcinogenic factor in PTC.

Overexpression of long non-coding RNA SBF2-AS1 promotes cell progression in esophageal squamous cell carcinoma (ESCC) by repressing miR-494 to up-regulate PFN2 expression.

Esophageal squamous cell carcinoma (ESCC) is an intractable esophageal cancer caused by smoking, alcohol consumption and nutritional deficiencies. Recently, long non-coding RNA SET-binding factor 2 antisense RNA 1 (SBF2-AS1) was validated as an oncogene in multiple cancers. However, the mechanism of SBF2-AS1 in ESCC progression is poorly understood. In the present research, we found that the expression of SBF2-AS1 and PFN2 was up-regulated, while miR-494 was down-regulated in ESCC tumors and cells using quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and transwell assay demonstrated that silencing of SBF2-AS1 suppressed proliferation, migration and invasion. Moreover, western blot showed that SBF2-AS1 deletion also inhibited epithelial to mesenchymal transition (EMT) by detecting MMP9, Vimentin and E-cadherin protein expression. We confirmed that miR-494 was a target of SBF2-AS1 by luciferase reporter system, RIP and RNA pull-down assay. In addition, miR-494 inhibitor reversed the repression induced by SBF2-AS1 silencing on ESCC cell proliferation, migration, invasion and EMT. Furthermore, PFN2 was negatively regulated by miR-494. Besides, restoration of PFN2 inversed the inhibition effects on cell proliferation, migration, invasion and EMT induced by SBF2-AS1 silencing in ESCC. In conclusion, SBF2-AS1 contributed to cell proliferation, migration, invasion and EMT in ESCC by enhancing PFN2 expression via sponging miR-494, providing promising biomarkers for ESCC diagnosis and treatment.