Background: Circular RNAs (circRNAs) are a class of non-coding RNA that play critical roles in the development and pathogenesis of various cancers. The circRNA circGSK3B (hsa_circ_0003763) has been shown to enhance cell proliferation, migration, and invasion in hepatocellular carcinoma. However, the specific functions and underlying mechanistic involvement of circGSK3B in gastric cancer (GC) have not yet been explored. Our study aimed to investigate the effect of circGSK3B on the progression of GC and to identify any potential mechanisms underlying this process. Methods: CircRNA datasets associated with GC were obtained from the PubMed, GEO, and ArrayExpress databases, and circRNAs were validated via RT-qPCR and Sanger sequencing. Biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, and in vitro binding assays were employed to determine proteins demonstrating interactions with circGSK3B. Gene expression regulation was assessed through RT-qPCR, chromatin immunoprecipitation, and western blot assays. Gain- and loss-of-function assays were used to analyze any effects of circGSK3B and its partner regulatory molecule (EZH2) on the proliferation, invasion, and migration abilities of GC cells both in vitro and in vivo. Results: CircGSK3B was mainly identified in the nucleus. This circRNA was present at a reduced concentration in GC tissues and cell lines. Overexpression of circGSK3B was shown to inhibit the growth, invasion, and metastasis of GC cells both in vitro and in vivo. Mechanistically, circGSK3B directly interacted with EZH2, acting to suppress the binding of EZH2 and H3K27me3 to the RORA promoter, and leading to an elevation in RORA expression and ultimately the suppression of GC progression. Conclusions: CircGSK3B acts as a tumor suppressor, reducing EZH2 trans-inhibition and GC progression. This demonstrates the potential use of this RNA as a therapeutic target for GC.

Gastric cancer is one of the most common malignant tumors, and it is also one of the leading causes of cancer death worldwide. Because of its insidious symptoms and lack of early dictation screening, many cases of gastric cancer are at late stages which make it more complicated to cure. For these advanced-stage gastric cancers, combination therapy of surgery, chemotherapy, radiotherapy and target therapy would bring more benefit to the patients. However, the drug-resistance to the chemotherapy restricts its effect and might lead to treatment failure. In this review article, we discuss the mechanisms which have been found in recent years of drug resistance in gastric cancer. And we also want to find new approaches to counteract chemotherapy resistance and bring more benefits to the patients.

The Wdr34 gene encodes an intermediate chain of cytoplasmic dynein 2, the motor for retrograde intraflagellar transport (IFT) in primary cilia. Although mutations in human WDR34 have recently been reported, the association of WDR34 function with Hedgehog (Hh) signaling has not been established, and actual cilia defects in the WDR34 mutant cells have also not been completely characterized. In the present study, we show that Wdr34 mutant mice die in midgestation and exhibit open brain and polydactyly phenotypes. Several Hh-dependent ventral neural cell types are not specified in the mutant neural tube. The expression of the direct Hh targets, Gli1 and Patched 1, is inhibited, while the expression of limb patterning genes that are normally inhibited by the Gli3 repressor is anteriorly expanded in mutant limbs. Comparison of cilia phenotype and function among wild type, Dnchc2 (dynein 2 heavy chain), and Wdr34 mutant cells demonstrates that cilia in both Dnchc2 and Wdr34 mutant cells are stumpy. Several ciliary proteins examined abnormally accumulate in the cilia of both mutant cells. Consistent with its function, overexpressed Wdr34 is occasionally localized to cilia, and Wdr34 is required for the ciliary localization of dynein 2 light intermediate chain Lic3. More interestingly, we show that both Dnchc2 and Wdr34 act between Smo and Gli2/Gli3 in the Hh pathway. Therefore, like Dnchc2, Wdr34 is required for ciliogenesis, retrograde ciliary protein trafficking, and the regulation of Gli2/Gli3 activators and repressors. Furthermore, both Wdr34 and Dnchc2 promote microtubule growth, a novel dynein 2 function in a non-cilia structure.

Background: Circular RNAs (circRNAs) are endogenous noncoding RNAs that play vital roles in many biological processes, particularly in human cancer. Recent studies indicate that circRNAs play an important role in tumor progression through exosomes. However, the specific functions of gastric cancer-derived exosomes and the role of circSTAU2 in gastric cancer (GC) remain largely unknown. Methods: Differentially expressed circRNAs in GC were identified by circRNA microarrays analysis and quantitative real-time polymerase chain reaction (qRT-PCR). The role of circSTAU2 in GC was verified by circSTAU2 knockdown and overexpression with functional assays both in vitro and in vivo. Fluorescence in situ hybridization (FISH), immunofluorescence, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, qRT-PCR and Western blot were adopted to evaluate the expression and regulatory mechanism of MBNL1, circSTAU2, miR-589 and CAPZA1. Furthermore, the role of exosomes was demonstrated by transmission electron microscopy and nano-sight particle tracking analysis. Results: CircSTAU2, mainly localized in the cytoplasm, was significantly downregulated in GC. CircSTAU2 overexpression inhibited GC cell proliferation, invasion and migration both in vitro and in vivo, while circSTAU2 knockdown had the inverse effect. CircSTAU2 could be wrapped in exosomes and delivered to recipient cells, and functioned as a sponge for miR-589 to relieve its inhibitory effect on CAPZA1, thus inhibiting GC progression. Furthermore, MBNL1 acted as the upstream RNA-binding protein of circSTAU2 and significantly influenced the circularization and expression of circSTAU2. Conclusion: Exosome-delivered circSTAU2 may act as a tumor suppressor that restrains GC progression via miR-589/CAPZA1 axis, which demonstrates a potential therapeutic target for GC.

Centrosomal protein 120 (CEP120) is a 120 kDa centrosome protein that plays an important role in centrosome replication. Overexpression of CEP120 can lead to centrosome duplicate abnormality, which is closely associated with tumorigenesis and development. However, there are no reports on the relationship between CEP120 and tumors. In our study, overexpression of CEP120 promoted centrosome amplification in gastric cancer (GC), and the role of CEP120 in promoting GC progression was demonstrated in vitro and in vivo. We demonstrated that CEP120 promotes centrosome amplification and GC progression by promoting the expression and centrosome aggregation of the deubiquitinating enzyme USP54, maintaining the stability of PLK4 and reducing its ubiquitination degradation. In conclusion, the CEP120-USP54-PLK4 axis may play an important role in promoting centrosome amplification and GC progression, thus providing a potential therapeutic target for GC.

The recent discovery of the pivotal role of the central nervous system in controlling tumor initiation and progression has opened a new field of research. Increasing evidence suggests a bidirectional interaction between the brain and tumors. The brain influences the biological behavior of tumor cells through complex neural networks involving the peripheral nervous system, the endocrine system, and the immune system, whereas tumors can establish local autonomic and sensory neural networks to transmit signals into the central nervous system, thereby affecting brain activity. This review aims to summarize the latest research in brain–tumor cross-talk, exploring neural circuitries between the brain and various peripheral solid tumors, analyzing the roles in tumor development and the related molecular mediators and pathologic mechanisms, and highlighting the critical impact on the understanding of cancer biology. Enhanced understanding of reciprocal communication between the brain and tumors will establish a solid theoretical basis for further research and could open avenues for repurposing psychiatric interventions in cancer treatment.