The Circular RNA circFOXK2 Enhances the Tumorigenesis of Non-Small Cell Lung Cancer Through the miR-149-3p/IL-6 Axis.

Circular RNAs (circRNAs) are the non-coding types of RNAs and are thoughts to be linked with human cancer progression. circFOXK2 is believed to be associated with cancers, however, the molecular mechanisms of circFOXK2 in non-small cell lung cancer (NSCLC) are still unclear. Here we firstly reported that circFOXK2 enhances the tumorigenesis of NSCLC through the miR-149-3p/IL-6 axis. The expression of circFOXK2, microRNA-149-3p (miR-149-3p) and IL-6 were assessed by qRT-PCR and western blot. Transwell, colony formation, wound healing, and CCK-8 assays were used to elucidate NSCLC cells' proliferation, migration, and invasion. MiR-149-3p interaction with circFOXK2 was confirmed by dual-luciferase reporter gene assay (DLRGA). Furthermore, the biological effect of circFOXK2 on NSCLC progression was detected by tumor xenograft assay. CircFOXK2 were upregulated in NSCLC tissues and cells, miR-149-3p were downregulated in NSCLC tissues and cells. In addition, circFOXK2 stimulated NSCLC cell proliferation, migration and invasion in vitro. Mechanical analysis indicated that circFOXK2 modulated IL-6 via miR-149-3p sponging. Furthermore, circFOXK2 overexpression promoted tumor growth in vivo. Overall, this research verified that circFOXK2 enhances the tumorigenesis of NSCLC through the miR-149-3p/IL-6 axis.

CircFOXK2 Promotes the Progression of Osteoarthritis by Regulating the miR-4640-5p/NOTCH2 Axis.

OBJECTIVE: Osteoarthritis (OA) is the most common age-related chronic and disabling joint disease, frequently causing pain and disability in the adult population. Given that there are no proven disease-modifying drugs for OA, it is urgent to gain a deeper understanding of OA pathogenesis. This study intended to uncover the circFOXK2 regulation in OA. METHODS: Firstly, in vitro OA cell model was constructed by treating murine chondrocytes with interleukin (IL)-1ß. Then, a series of functional assays were conducted to evaluate the effect of circFOXK2 on OA progression in murine chondrocytes. Bioinformatics analysis and mechanism investigations were performed to investigate the competitive endogenous RNA (ceRNA) network of circFOXK2 in OA. RESULTS: CircFOXK2 is overexpressed in IL-1ß-treated chondrocyte. We confirmed the cyclic structure and cytoplasmic distribution of circFOXK2. Functionally, circFOXK2 promotes chondrocyte apoptosis and extracellular matrix (ECM) degradation but inhibiting chondrocyte proliferation. Mechanically, circFOXK2 competitively binds to microRNA-4640-5p (miR-4640-5p) to enhance NOTCH2 expression in OA, affecting OA progression. Besides, circFOXK2 could motivate the Notch pathway to accelerate OA progression. CONCLUSION: CircFOXK2/miR-4640-5p/NOTCH2 axis stimulates the Notch pathway to promote the transcription of inflammatory cytokines (IL33, IL17F and IL6), consequently facilitating OA progression in murine chondrocytes.

CircRNA circFOXK2 facilitates oncogenesis in breast cancer via IGF2BP3/miR-370 axis.

Metastasis is the leading cause of breast cancer (BC)-related deaths. Circular RNAs (circRNAs) have emerged as essential regulators for cancer progression and metastasis. Therefore, the objective of this study was to investigate the role of circRNAs in BC metastasis and related mechanism. In this study, we established the BC cell line with high or low potential of metastasis. RNA sequencing, migration and invasion assay, Fluorescence in situ hybridization, luciferase report assay, circRNA pulldown, and transmission electron microscopy were performed to elucidate the molecular mechanism. The results showed that circRNA circFOXK2 was significantly increased in BC cells with high metastatic ability, and the upregulation of circFOXK2 was correlated with poor clinicopathological characteristics. Functional experiments demonstrated that overexpression of circFOXK2 promoted migration and invasion of BC cells. Also. circFOXK2 could act with IGF2BP3, an RNA-binding protein, and miR-370 to synergistically promote BC metastasis. Moreover, miR-370 could be transferred through exosomes to enhance the metastatic ability of recipient cells. In conclusion, circFOXK2 functions as a key regulator in BC metastasis, and the role of circFOXK2 on BC metastasis is tightly associated with the involvement of IGF2BP3 and miR-370. CircFOXK2 might serve as a potential biomarker for the diagnosis and treatment of BC.