Circ_PRKCA Drove NSCLC Progression via SRSF1/HIF-1A/PKM2 Axis-Mediated Glycolytic Reprogramming.

CircATRNL1 Facilitates Malignant Progression of Non–Small Cell Lung Cancer via the miR-103a-3p/IGFBP3/PI3K-AKT Axis

: Background: Circular RNAs have emerged as important regulators of non-small cell lung cancer progression through competing endogenous RNA networks, but the specific role and mechanism of CircATRNL1 in NSCLC remain unclear. This study investigates the mechanistic role of CircATRNL1 in the malignant progression of non-small cell lung cancer (NSCLC). Methods: Gene expression levels in NSCLC cell lines were quantified using reverse transcription quantitative PCR (RT-qPCR). Functional assays, including Western blot analysis of epithelial– mesenchymal transition (EMT)-related proteins, wound-healing assays, and Transwell migration and invasion assays, were performed to assess the effects of CircATRNL1 on cellular motility and invasive potential. Potential RNA–RNA interactions were predicted using the ENCORI and CircBank databases, followed by luciferase reporter assays to validate these interactions experimentally. To determine whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway mediated the biological effects of insulin-like growth factor-binding protein 3 (IGFBP3), rescue experiments were performed using the PI3K inhibitor LY294002. Results: CircATRNL1 was significantly upregulated in NSCLC cell lines and showed typical circular RNA characteristics, including RNase R resistance and enhanced transcript stability (*** p < 0.001). CircATRNL1 knockdown inhibited NSCLC cell migration and invasion, whereas CircATRNL1 overexpression exerted the opposite effects. Mechanistically, CircATRNL1 functioned as a sponge for miR-103a-3p and relieved miR-103a-3p mediated repression of IGFBP3, as validated by luciferase reporter and rescue assays (** p < 0.01). IGFBP3 further activated PI3K/AKT signaling by increasing p-PI3K/PI3K and p-AKT/AKT ratios, while LY294002 attenuated IGFBP3-induced migration and invasion. Conclusions: CircATRNL1 promotes NSCLC cell migration and invasion by acting as a ceRNA for miR-103a-3p, thereby regulating IGFBP3 and activating PI3K/AKT signalling. These findings highlight the CircATRNL1/miR-103a-3p/IGFBP3/PI3K-AKT axis as a potential regulatory mechanism contributing to in vitro migration and invasion in NSCLC.

CircUBE2I regulates YAP/TAZ signaling pathway through miR-659-3p/PSMA1 axis to promote human lung adenocarcinoma cell progression.

Circular RNAs (circRNAs) exhibit wide expression across human tissues and play pivotal roles in tumorigenesis and cancer progression. However, studies regarding the function and mechanism of circRNAs in lung adenocarcinoma (LUAD) are insufficient, it needs to be further explored. This investigation aimes to describe dysregulated circRNAs in LUAD, elucidate their functional roles in tumor progression, and establish novel molecular targets for diagnostic and therapeutic applications in pulmonary malignancies. Functional studies were performed to clarify the regulatory effects of circUBE2I on LUAD progression in vitro and in vivo. To elucidate the molecular mechanisms of circUBE2I, we performed dual-luciferase reporter assays, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and Chromatin Isolation by RNA Purification (ChIRP). CircUBE2I expression was up-regulated in LUAD tissues, plasma, and cell lines. CircUBE2I is crucial in the proliferation, migration, and regulation of the cell cycle in lung cancer cells in vitro. Subsequent mechanistic investigations showed that circUBE2I functions as a competitive endogenous RNA (ceRNA). It can effectively sequester miR-659-3p, thus reducing its inhibitory effect on PSMA1 expression. This molecular interaction ultimately activates the yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) pathway. In conclusion, our findings demonstrate that circUBE2I is a novel circRNA that promotes LUAD cells proliferation and migration by modulating the YAP/TAZ signaling pathway through the miR-659-3p/PSMA1 axis, suggesting its potential as both a diagnostic biomarker and therapeutic target for LUAD.

Circ17399 RNA promotes melanoma progression through the miR-150-3p/ITM2C Axis and ALKBH5-mediated FOXM1 m6A modification

Skin cutaneous melanoma (SKCM) is a highly aggressive malignancy with a poor prognosis, necessitating the exploration of novel molecular mechanisms driving its progression. CircRNA, which have emerged as critical regulators in cancer biology, have been implicated in various tumorigenic processes. However, their specific roles in SKCM remain inadequately understood. Bioinformatics analyses of TCGA and GEO datasets identified circ17399 as a candidate oncogenic circRNA. Functional validation was performed using in vitro (A375, A2058 cells) and in vivo models. Techniques included qRT-PCR, dual-luciferase reporter assays, RNA FISH, Western blot, Transwell assays, and MeRIP-qPCR. Circ17399 knockdown/overexpression, miR-150-3p modulation, and ALKBH5/FOXM1 interaction studies were conducted to dissect its regulatory network. Circ17399 was significantly upregulated in SKCM tissues and correlated with poor prognosis. Mechanistically, circ17399 sponged miR-150-3p to derepress ITM2C, enhancing SKCM cell proliferation, migration, and invasion. Concurrently, circ17399 bound ALKBH5, reducing m6A methylation on FOXM1 mRNA, thereby stabilizing FOXM1 and promoting tumor progression. In vivo, circ17399 knockdown suppressed tumor growth and metastasis, while overexpression exacerbated malignancy. Circ17399 promotes melanoma progression by competitively binding miR-150-3p to upregulate ITM2C and recruiting ALKBH5 to reduce m6A methylation of FOXM1, enhancing its stability and oncogenic function. These findings unveil a dual-axis regulatory mechanism in SKCM pathogenesis and position circ17399 as a promising diagnostic biomarker and actionable therapeutic target for melanoma intervention.

CircGABRB2_006 Drives Malignant Progression and EMT in Papillary Thyroid Carcinoma via the miR-296-5p/FGFR1 Axis.

Identification and validation of NCOA5-ZCCHC3/FGF22 axis as a prognostic marker in lung adenocarcinoma migration and invasion

Lung adenocarcinoma (LUAD), the most common subtype of lung cancer, is associated with substantial global mortality. Nuclear receptor coactivator 5 (NCOA5) has been implicated in several malignancies; however, its functional role and regulatory mechanisms in LUAD remain largely unknown. In this study, NCOA5 expression was evaluated in 94 paired LUAD and adjacent tissues using immunohistochemistry, RT-PCR, and Western blotting. Functional analyses were conducted using shRNA knockdown, CRISPR-mediated knockout, and overexpression models to assess the effects of NCOA5 on LUAD cell proliferation, migration, invasion, apoptosis, cell cycle progression, and organoid formation. Xenograft models were used to validate tumorigenicity in vivo. IP-MS and co-immunoprecipitation identified NCOA5-interacting proteins, while ChIP-seq and dual-luciferase assays interrogated downstream transcriptional regulation. NCOA5 was significantly upregulated in LUAD tissues and associated with advanced stage, poor differentiation, and reduced overall survival, serving as an independent prognostic factor ( P  < .040). NCOA5 knockdown inhibited LUAD cell proliferation, migration, invasion, induced G0/G1 arrest, promoted apoptosis, reduced organoid formation, and suppressed xenograft growth, whereas NCOA5 overexpression produced the opposite effects. Among 39 candidate interacting proteins identified by IP-MS, ZCCHC3 was validated as a direct NCOA5-binding partner. ZCCHC3 depletion phenocopied NCOA5 loss and reversed NCOA5-induced proliferation, migration, invasion, and colony formation, supporting a functional NCOA5–ZCCHC3 interaction. ChIP-seq analysis identified fibroblast growth factor 22 (FGF22) as a direct transcriptional target of NCOA5. FGF22 was markedly downregulated in LUAD tissues and higher FGF22 expression was associated with improved patient survival. NCOA5 suppressed FGF22 transcription, while NCOA5 inhibition increased FGF22 expression. Functionally, FGF22 knockdown enhanced LUAD aggressiveness, whereas FGF22 restoration abrogated the oncogenic effects of NCOA5 in vitro and in vivo. Collectively, these findings identify a previously unrecognized NCOA5–ZCCHC3/FGF22 axis that drives LUAD progression and provide new mechanistic insight into the role of NCOA5 in LUAD biology.

A novel peptide encoded by circTLL1 drives osimertinib resistance in lung cancer by modulating the NT5C2/Ras/PI3K axis.

The identification of the circTLL1-90aa/NT5C2/Ras/PI3K axis not only expands the functional repertoire of the non-coding genome but also provides new insights into the complexity of drug resistance.