Background: Glioblastoma (GBM) is the most aggressive brain tumor. Reportedly, circular RNAs (circRNAs) participate in regulation of the development and progression of diverse cancers, including GBM.Methods: Dysregulated circRNAs in GBM tissues were screened out from GEO database. The expression of candidate circRNAs in GBM cells was measured by qRT‐PCR. Loss‐of function assays, including colony formation assay, EdU assay, TUNEL assay, and flow cytometry analysis were conducted to determine the effects of circ‐AHCY knockdown on GBM cell proliferation and apoptosis. Animal study was further used to prove the inhibitory effect of circ‐AHCY silencing on GMB cell growth. Mechanistic experiments like luciferase reporter, RNA pull‐down and RNA‐binding protein immunoprecipitation (RIP) assays were performed to unveil the downstream molecular mechanism of circ‐AHCY. Nanosight Nanoparticle Tracking Analysis (NTA) and PKH67 staining were applied to identify the existence of exosomes.Results: Circ‐AHCY was confirmed to be highly expressed in GBM cells. Circ‐AHCY silencing suppressed GBM cell proliferation both in vitro and in vivo. Mechanistically, circ‐AHCY activates Wnt/β‐catenin signaling pathway by sequestering miR‐1294 to up‐regulate MYC which activated CTNNB1 transcription. It was also found that circ‐AHCY recruited EIF4A3 to stabilize TCF4 mRNA. Enhanced levels of TCF4 and β‐catenin contributed to the stability of TCF4/β‐catenin complex. In turn, TCF4/β‐catenin complex strengthened the transcriptional activity of circ‐AHCY. Exosomal circ‐AHCY derived from GBM cells induced abnormal proliferation of normal human astrocytes (NHAs).Conclusion: Exosomal circ‐AHCY forms a positive feedback loop with Wnt/β‐catenin signaling pathway to promote GBM cell growth.

Pituitary adenomas (PAs) are the second most common primary brain tumor and may develop from any of the cell lineages responsible for producing the different pituitary hormones. DNA methylation is one of the essential epigenetic mechanisms in cancers, including PAs. In this study, we measured the expression profile and promoter methylation status of carbohydrate sulfotransferase 7 (CHST7) in patients with PA; then, we investigated the effect of the CHST7 methylation status on the proliferation and differentiation of PAs. The volcano map and Metascape results showed that the levels of CHST7 were related to the lineages’ differentiation and the cell adhesion of PAs, and patients with low CHST7 had greater chances of having an SF-1 lineage (p = 0.002) and optic chiasm compression (p = 0.007). Reactome pathway analysis revealed that most of the DEGs involved in the regulation of TP53 regulated the transcription of cell cycle genes (HSA-6791312 and HSA6804116) in patients with high CHST7. Correlation analysis showed that CHST7 was significantly correlated with the eIF2/ATF4 pathway and mitochondrion-related genes. The AUC of ROC showed that CHST7 (0.288; 95% CI: 0.187–0.388) was superior to SF-1 (0.555; 95% CI: 0.440–0.671) and inferior to FSHB (0.804; 95% CI: 0.704–0.903) in forecasting the SF-1 lineage (p < 0.001). The SF-1 lineage showed a higher methylation frequency for CHST7 than the Pit-1 and TBX19 lineages (p = 0.009). Furthermore, as the key molecule of the hypothalamic–pituitary–gonadal axis, inhibin βE (INHBE) was positively correlated with the levels of CHST7 (r = 0.685, p < 0.001). In summary, CHST7 is a novel pituitary gland specific protein in SF-1 lineage adenomas with a potential role in gonadotroph cell proliferation and lineage differentiation in PAs.

Recent studies indicate that circular RNAs (circRNAs) are crucial in the progression of colorectal cancer (CRC). Eukaryotic translation initiation factor 4A3 (EIF4A3) has been identified as a promoter of circRNA production. The biological roles and mechanisms of EIF4A3-derived circRNA (circEIF4A3) in CRC cell autophagy remain poorly understood. This study explores the effects of circEIF4A3 on CRC cell growth and autophagy, aiming to elucidate the underlying molecular mechanisms. We discovered that EIF4A3 and circEIF4A3 synergistically enhance CRC cell growth. CircEIF4A3 sequesters miR-3126-5p, consequently upregulating EIF4A3. Further, circEIF4A3 increases EIF4A3 expression, which promotes autophagy by stabilizing ATG5 mRNA and enhances ATG7 protein stability through the stabilization of USP14 mRNA, a deubiquitinating enzyme. Upregulation of ATG5 and ATG7 counteracts the growth-inhibitory effects of EIF4A3 knockdown on CRC cells. Moreover, our findings demonstrate that EIF4A3 induces the formation of circEIF4A3 in CRC cells. In conclusion, a positive feedback loop between circEIF4A3 and EIF4A3 supports CRC cell growth by facilitating autophagy.

The aim of the present study was to develop and evaluate a clinical‑imaging‑radiomic nomogram based on pre‑enhanced computed tomography (CT) for pre‑operative differentiation lipid‑poor adenomas (LPAs) from metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas (AIs). A total of 196 consecutive patients with lung cancer, who underwent initial chest or abdominal pre‑enhanced CT scan with small hyperattenuating AIs, were included. The patients were randomly divided into a training cohort with 71 cases of LPAs and 66 cases of metastases, and a testing cohort with 31 cases of LPAs and 28 cases of metastases. Plain CT radiological and clinical features were evaluated, including sex, age, size, pre‑enhanced CT value (CT_pre), shape, homogeneity and border. A total of 1,316 radiomic features were extracted from the plain CT images of the AIs, and the significant features selected by the least absolute shrinkage and selection operator were used to establish a Radscore. Subsequently, a clinical‑imaging‑radiomic model was developed by multivariable logistic regression incorporating the Radscore with significant clinical and imaging features. This model was then presented as a nomogram. The performance of the nomogram was assessed by calibration curves and decision curve analysis (DCA). A total of 4 significant radiomic features were incorporated in the Radscore, which yielded notable area under the receiver operating characteristic curves (AUCs) of 0.920 in the training dataset and 0.888 in the testing dataset. The clinical‑imaging‑radiomic nomogram incorporating the Radscore, CT_pre, sex and age revealed favourable differential diagnostic performance (AUC: Training, 0.968; testing, 0.915) and favourable calibration curves. The nomogram was revealed to be more useful than the Radscore and the clinical‑imaging model in clinical practice by DCA. The clinical‑imaging‑radiomics nomogram based on initial plain CT images by integrating the Radscore and clinical‑imaging factors provided a potential tool to effectively differentiate LPAs from metastases in patients with lung cancer with small hyperattenuating AIs.