CircFut8 Suppresses Bladder Cancer by Modulating SRSF9‐Dependent Pre‐mRNA Splicing

Circ_0001495 promotes bladder cancer progression by regulating miR-1184 via MAPK signaling pathway

Splicing-mediated control of hnRNPD isoform switching by SRSF2 drives PD-L1-dependent immune evasion in gallbladder cancer

A specific protein (SRSF2) acts like a rogue editor, altering the genetic instructions of another molecule (hnRNPD) and creates a “shield” (PD-L1) on the surface of the cancer cell, effectively blinding the immune system and allowing the tumor to grow unchecked.

CircBRWD3 promotes non-small cell lung cancer progression through enhancing the stability of TRIM25 to increase p53 ubiquitin degradation and upregulating SPTBN2.

Circular RNAs (circRNAs) play crucial roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear. In this study, we found a novel circRNA, hsa_circ_0001936(circBRWD3), in NSCLC and investigated the biological role of circBRWD3 in NSCLC progression in vitro and in vivo. qRT-PCR was used to quantify the expression of circBRWD3 in NSCLC tissues, serum and cells. Cell growth curves, colony formation, Edu assay and transwell assays were conducted to study the function of circBRWD3. Finally, the molecular mechanism of circBRWD3 was revealed by Bioinformatic analyses, RNA pull-down analysis, RNA Fluorescence in situ hybridization (FISH), RNA-Binding Protein Immunoprecipitation (RIP), western blot, dual-luciferase reporter gene assays and rescue experiments. Our results showed that circBRWD3 was upregulated in NSCLC tumor tissues, patient serum and cell lines. CircBRWD3 knockdown inhibited NSCLC cells' growth and metastasis both in vitro and in vivo, while circBRWD3 overexpression had the opposite effect. Mechanistically, circBRWD3 binds to the TRIM25 protein to enhance its stability and mediate ubiquitin degradation of the p53 protein. In addition, circBRWD3 acted as a sponge for miR-135a-5p and miR-135b-5p to regulate the expression of SPTBN2, which promoted NSCLC progression. Our findings uncovered a tumor oncogenic function of circBRWD3 in NSCLC through the regulation of TRIM25 protein stability and miR-135a-5p/miR-135b-5p/SPTBN2 axis. CircBRWD3 may act as a promising oncogenic biomarker and therapeutic target for 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.

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

Elucidating the complex molecular drivers of non-small cell lung cancer (NSCLC) and identifying novel therapeutic targets are urgently needed. Although circPRKCA is implicated in tumorigenesis, its role in NSCLC remains poorly characterized. This study investigates the biological functions and regulatory mechanisms of circPRKCA in NSCLC. CircPRKCA expression and downstream target expression were assessed via qRT-PCR and Western blotting. In vitro functional assays evaluated circPRKCA's role in NSCLC cells. Regulatory mechanisms were further examined using database analysis, RNA immunoprecipitation (RIP), and dual-luciferase reporter assays. In vivo tumor growth was evaluated in mouse xenograft models. CircPRKCA was significantly upregulated in NSCLC and promoted tumor growth and metastasis. Our data suggest that circPRKCA may act as a scaffold for RNA-binding proteins (RBPs), potentially facilitating the recruitment of SRSF1 to HIF-1A mRNA, which appeared to correlate with increased HIF-1A stability. HIF-1A overexpression enhanced NSCLC cell proliferation via PKM2-mediated glycolysis. High circPRKCA expression correlated with poor survival in NSCLC patients. CircPRKCA-SRSF1 axis enhanced proliferation and suppressed apoptosis by stabilizing HIF-1A and modulating PKM2-driven glycolysis. These findings reveal novel diagnostic biomarkers and therapeutic strategies for NSCLC.

Circular RNA circEVI5 functions as a miR-433 sponge to promote renal cell carcinoma progression via GBP2-mediated oncogenic signaling

Introduction Renal cell carcinoma (RCC) is a fatal urological malignancy with limited therapeutic options and poor prognosis. Emerging evidence has shown that a number of circular RNAs (circRNAs) exert crucial effects on carcinogenesis. Nevertheless, the biological role of circEVI5 in RCC remains poorly clarified. This study aimed to elucidate the clinical significance, biological functions, and molecular mechanisms of circEVI5 in RCC pathogenesis. Methods The expression profile of circEVI5 was first screened based on GEO and TCGA-KIRC datasets, and further verified in RCC cell lines (A498, 786-O, ACHN, CAKI-1, OSRC-2) and normal renal tubular epithelial HK-2 cells using qRT-PCR. Functional assays (CCK-8, Transwell) and a subcutaneous xenograft model were employed to assess circEVI5’s role in proliferation, migration, and invasion. RNA pull-down, RIP, and dual-luciferase reporter assays were conducted to validate interactions among circEVI5, miR-433, and GBP2. Clinical correlations were further analyzed based on TCGA datasets and immunohistochemical staining results. Results CircEVI5 was significantly upregulated in RCC tissues (median FC=6.619; P<0.05) and cell lines, correlating with advanced tumor stage (median FC=7.691; P<0.05) and poor survival (P=0.035). Knockdown of circEVI5 via small interfering RNA inhibited cell viability, migration, and invasion in vitro and suppressed tumor growth in vivo. Mechanistically, circEVI5 acted as a cytoplasmic molecular sponge for miR-433, which was downregulated in RCC and inversely correlated with GBP2 expression. RNA pull-down and RIP assays confirmed direct binding between circEVI5 and miR-433, while luciferase assays identified GBP2 as a miR-433 target. Rescue experiments demonstrated that miR-433 inhibition or recombinant GBP2 reversed the anti-tumor effects of circEVI5 knockdown. Clinically, GBP2 overexpression in RCC tissues predicted reduced survival, and miR-433 levels were inversely correlated with both circEVI5 (P<0.0001) and GBP2 (P=0.0003). Discussion Our findings establish circEVI5 as a novel oncogenic driver that facilitates RCC progression through the miR-433/GBP2 regulatory axis. The circEVI5/miR-433/GBP2 network represents a potential therapeutic target, and circEVI5 may serve as a prognostic biomarker for RCC patients. This study highlights the critical role of circRNA-mediated miRNA sponging in RCC pathogenesis and provides a framework for developing RNA-based therapies.