Background: Circular RNAs(circRNAs) have been reported as a diverse class of endogenous RNA that regulate gene expression in eukaryotes. Recent evidence suggested that many circular RNAs can act as oncogenes or tumor suppressors through sponging microRNAs. However, the function of circular RNAs in gastric cancer remains largely unknown. Materials and methods: The circRNA levels in gastric carcinoma tissues and plasmas were detected by real-time quantitative reverse transcription-polymerase chain reaction. The correlation between the expression of circRNA and clinic pathological features was analyzed. Rate of inhibiting of proliferation was measured using a CCK-8 cell proliferation assay. Clone formation ability was assessed with a clone formation inhibition test. We used the bioinformatics software to predict circRNA-miRNA and miRNA-mRNA interactions. Relative gene expression was assessed using quantitative real-time polymerase chain reaction and relative protein expression levels were determined with western blotting. CircRNA and miRNA interaction was confrmed by dual-luciferase reporter assays. Results: We characterized that one circRNA named circ-SFMBT2 showed an increased expression level in gastric cancer tissues compared to adjacent non-cancerous tissues and was associated with higher tumor stages of gastric cancer. Silencing of circ-SFMBT2 inhibited the proliferation of gastric cancer cells significantly. Importantly, we demonstrated that circ-SFMBT2 could act as a sponge of miR-182-5p to regulate the expression of CREB1 mRNA, named as cAMP response element binding protein 1, and further promote the proliferation of gastric cancer cells. Conclusion: Our study reveals that circ-SFMBT2 participates in progression of gastric cancer by competitively sharing miR-182-5p with CREB1, providing a novel target to improve the treatment of gastric cancer. mutation-analysis-of-beta-thalassemia-in-east-western-indian-populatio-peer-reviewed-article-TACG for an example.

Circular RNAs (circRNAs), a novel family of non-coding RNAs, play crucial roles in cancer progression. While the existing research focuses on nuclear genome-derived (nu)-circRNAs, the biological and clinical characteristics of mitochondrial genome-derived (mt)-circRNAs remain largely unknown, especially in chronic lymphocytic leukemia (CLL). In this study, we attempted to identify the novel characteristics of mc-COX2 (mitochondrial genome-derived circRNAs [mc]), one of the mt-circRNAs that can be involved in CLL progression. mt-circRNAs were found to be highly expressed in the plasma exosomes of CLL patients. The endogenous reduction of mc-COX2 can affect mitochondrial functions, suppress cell proliferation, and induce cell apoptosis. The upregulation of mc-COX2 was positively associated with leukemogenesis and worsening survival of CLL patients. Notably, functional analysis revealed that mc-COX2, as differing from conventional nu-circRNAs, was less stable and may function through novel mechanisms other than acting as the competing endogenous RNA. We also screened and tested several chemical compounds and small-molecule inhibitors that can decrease the generation of mc-COX2. It was found that the silencing of mc-COX2 in CLL cells strengthened the anti-tumor effects of drugs used in coordination. Our findings prove that mc-COX2, a critical mt-circRNA highly expressed in plasma, derived from CLL cells and delivered by exosomes, is associated with the progression and prognosis of CLL.

Circular RNA (circRNA) is a key regulator in the development and progression of various types of carcinomas. However, its role in gastric cancer (GC) tumorigenesis is not well understood. The present study aimed to investigate the expression profile and potential modulation of circRNAs on GC carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in GC tissue. Results showed that a decrease in the circPVRL3 expression level was associated with the presence of GC, and also with higher TNM stage and lower overall survival rates compared with that in adjacent noncancerous tissues. In vitro assays of the GC cell lines MKN-45 and MGC-803 demonstrated that knockdown of circPVRL3 promoted cell proliferation significantly. Prediction and annotation revealed circPVRL3 was able to sponge to 9 miRNAs and may be also able to have a binding with AGO2, FUS, LIN28A, PTB, and EIF4A3. In addition, based on the structure of internal ribosomal entry sites, open reading frame, and m⁶A modification, circPVRL3 may have the potential ability to encode proteins. Taken together, our study indicated that down-regulation of circPVRL3 could promote the proliferation in gastric carcinoma and have potential to encode protein.

Chronic lymphocytic leukemia (CLL) is a hematological malignancy with high metabolic heterogeneity. N6‐methyladenosine (m6A) modification plays an important role in metabolism through regulating circular RNAs (circRNAs). However, the underlying mechanism is not yet fully understood in CLL. Herein, an m6A scoring system and an m6A‐related circRNA prognostic signature are established, and circTET2 as a potential prognostic biomarker for CLL is identified. The level of m6A modification is found to affect the transport of circTET2 out of the nucleus. By interacting with the RNA‐binding protein (RBP) heterogeneous nuclear ribonucleoprotein C (HNRNPC), circTET2 regulates the stability of CPT1A and participates in the lipid metabolism and proliferation of CLL cells through mTORC1 signaling pathway. The mTOR inhibitor dactolisib and FAO inhibitor perhexiline exert a synergistic effect on CLL cells. In addition, the biogenesis of circTET2 can be affected by the splicing process and the RBPs RBMX and YTHDC1. CP028, a splicing inhibitor, modulates the expression of circTET2 and shows pronounced inhibitory effects. In summary, circTET2 plays an important role in the modulation of lipid metabolism and cell proliferation in CLL. This study demonstrates the clinical value of circTET2 as a prognostic indicator as well as provides novel insights in targeting treatment for CLL.

Circular RNAs (circRNAs) have recently been reported to play crucial roles in various regulatory processes and involved in cancer onset and progression. However, the potential mechanism of circRNAs in chronic lymphocytic leukemia (CLL) remains largely unknown. Here, we observed hsa_circ_0132266 (circ_0132266), a circRNA significantly decreased in the peripheral blood mononuclear cells (PBMCs) of CLL patients compared with healthy donors, could act as an endogenous sponge of hsa-miR-337-3p (miR-337-3p) and regulate its activity, which resulted in a downstream change of target-gene PML and a consequent influence on cell viability. Taken together, our data indicated the regulatory mechanism of circ_0132266 in CLL progression through circ_0132266/miR-337-3p/PML axis, suggesting that it may serve as a biomarker as well as an exploitable therapeutic target for CLL.