An Evaluation of Paddy Rice as an Alternative Energy Source in Protein-Restricted Diets for Growing, Early-Finishing, and Late-Finishing Pigs.

Three experiments were conducted to evaluate paddy rice as an alternative energy feedstuff in low-protein diets for pigs. In Experiment 1, a total of 400 growing pigs (20.68 ± 0.29 kg initial bodyweight), were randomly allocated four dietary treatments with 0, 10, 15, and 20% paddy rice for 30 days. Feeding 10% or 15% paddy rice had no adverse impacts on average daily gain (ADG) and feed to gain ratio (F:G), while the inclusion of 20% rice in diets significantly influenced the growth performance of pigs. In Experiment 2, 364 early-finishing pigs (42.25 ± 0.47 kg) were divided into four treatments with 0, 15, 20, and 25% paddy rice for 35 days. Feeding 15% or 20% paddy rice had no negative consequences on growth performance, while pigs fed with 25% rice had the lowest ADG and the greatest F:G. In Experiment 3, 364 late-finishing pigs (79.52 ± 1.28 kg) were divided into four treatments with 0, 20, 25, and 30% paddy rice for 60 days. Paddy rice can be included at up to 30% in diets without compromising growth performance, while feeding with 25% rice significantly improved the performance for pigs compared with the corn-fed control.

Targeting the cGAS-STING Pathway Inhibits Peripheral T-cell Lymphoma Progression and Enhances the Chemotherapeutic Efficacy.

Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous group of mature T-cell malignancies. The efficacy of current first-line treatment is dismal, and novel agents are urgently needed to improve patient outcomes. A close association between the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway and tumor promotion exists, revealing prospective therapeutic targets. This study, investigates the role of the cGAS-STING pathway and its underlying mechanisms in PTCL progression. Single-cell RNA sequencing showes that the cGAS-STING pathway is highly expressed and closely associated with PTCL proliferation. cGAS inhibition suppresses tumor growth and impaires DNA damage repair. Moreover, Cdc2-like kinase 1 (CLK1) is critical for residual tumor cell survival after treatment with cGAS inhibitors, and CLK1 suppression enhances sensitivity to cGAS inhibitors. Single-cell dynamic transcriptomic analysis indicates reduced proliferation-associated nascent RNAs as the underlying mechanism. In first-line therapy, chemotherapy-triggered DNA damage activates the cGAS-STING pathway, and cGAS inhibitors can synergize with chemotherapeutic agents to kill tumors. The cGAS-STING pathway is oncogenic in PTCL, whereas targeting cGAS suppresses tumor growth, and CLK1 may be a sensitivity indicator for cGAS inhibitors. These findings provide a theoretical foundation for optimizing therapeutic strategies for PTCL, especially in patients with relapsed/refractory disease.

m6A-Modified circTET2 Interacting with HNRNPC Regulates Fatty Acid Oxidation to Promote the Proliferation of Chronic Lymphocytic Leukemia.

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.

Expression Profile of miR-199a and Its Role in the Regulation of Intestinal Inflammation.

Early weaning stress impairs intestinal health in piglets. miRNAs are crucial for maintaining host homeostasis, while their implication for animal health remains unclear. To identify weaning-associated miRNAs, piglets were sampled at day 0, 1, 3, 7 and 14 after weaning. The data indicated that the highest levels of miR-199a-5p in jejunal villus upper cells were observed on day 14 after weaning, while the lowest levels in crypt cells were noted on day 7 and 14. In contrast, miR-199a-3p was down-regulated in both of these two cells on day 7 after weaning compared with day 0. Both miR-199a-5p and -3p were differently expressed along the villus-crypt axis. To further clarify the function of miR-199a, mice deficient in miR-199a were exposed to dextran sulfate sodium (DSS) to induce colitis. Results revealed that silencing of miR-199a enhanced sensitivity to DSS-induced colitis. Moreover, the increased morbidity and mortality were correlated with enhanced inflammatory cell infiltration, elevated pro-inflammatory cytokine expression, impaired barrier function, and a concomitant increase in permeability-related parameters. Bioinformatic analysis further demonstrated that lipid metabolism-related pathways were significantly enriched and Ndrg1 was verified as a target of miR-199a-3p. These findings indicate that miR-199a may be important for animal health management.

Investigation of the Expression Pattern and Functional Role of miR-10b in Intestinal Inflammation.

Implications of miRNAs for animal health management in livestock remain elusive. To identify suitable miRNAs as monitoring biomarkers, piglets were randomly selected for sampling on days 0, 1, 3, 7, and 14 post-weaning. The results show that miR-10b levels in the villus upper cells of the jejunum on days 3 and 7 were significantly lower than that on day 14 post-weaning and reduced by approximately 30% on day 3 and 55% on day 7 compared to day 0. In contrast, miR-10b in crypt cells decreased by approximately 82% on day 7 and 64% on day 14 compared with day 0. Next, miR-10 knockout mice and wild-type mice were subjected to dextran sulfate sodium (DSS) for 7 days. The findings demonstrate that mice lacking miR-10b were more susceptible to DSS administration, as demonstrated by worse survival, greater weight loss, more severe tissue damage, and increased intestinal permeability. Moreover, the increased disease severity was correlated with enhanced macrophage infiltration, coincident with significantly elevated pro-inflammatory mediators and immunoglobulins. Bioinformatic analysis further reveals that the enriched pathways were mainly involved in host immune responses, and Igtp was identified as a potential target of miR-10b. These findings may provide new strategies for future interventions for swine health and production.

Multiple amino acid supplementations to reduce dietary protein for pigs during early and late finisher periods under commercial conditions.

BACKGROUND: With the easy availability and competitive prices of crystalline amino acids (AAs), the reduction of dietary crude protein (CP) for pigs during early and late finisher periods is possible under commercial conditions. Two experiments were conducted to assess the growth efficiency of early and late-finishing pigs fed with protein-restricted diets supplemented with Lys, Met, Thr, Trp, Val, Ile and His. In Experiment 1, 840 early finishing pigs were allocated to four dietary treatments with CP levels designed at 150, 142, 134, and 126 g kg-1 diet. In Experiment 2, 768 late-finishing pigs were allotted to four dietary treatments providing CP levels at 140, 130, 120, and 110 g kg-1 diet. RESULTS: In Experiment 1, the data showed that CP levels could be decreased from 150 to 126 g kg-1 without adversely affecting performance of early finishing pigs as no significant difference was observed for final bodyweight, average daily gain (ADG), feed to gain ratio (F:G), or average daily feed intake (ADFI). In Experiment 2, late-finishing pigs consuming 120 g kg-1 CP tended to have the highest ADG and lowest F:G whereas those fed the 110 g kg-1 CP diet showed the opposite trend. Based on quadratic analysis, the optimum CP levels to maximize ADG and minimize F:G were 126 and 127 g kg-1 , respectively. CONCLUSION: These findings showed that dietary CP levels could be decreased to 126 g kg-1 for early finishing pigs while improved performance was noted in late-finishing pigs consuming 120 g kg-1 CP. © 2023 Society of Chemical Industry.

Effect of pharmacist intervention on antibiotic prophylaxis in orthopedic internal fixation: A retrospective study.

BACKGROUND: Despite the availability of guidelines and official policies, antibiotic prophylaxis in clean surgery remains suboptimal. OBJECTIVE: The aim of this study was to evaluate the clinical effects and cost-effectiveness of pharmacist-led intervention in the perioperative anti-infection prophylaxis of patients undergoing orthopedic internal fixation. METHODS: We performed a retrospective analysis based on the medical records of internal fixation surgery in a tertiary hospital from July 2019 to June 2020. Data were divided into two groups based on whether a full-time pharmacist participated in the treatment. The research parameters included use of antibiotics, rationality of medication, postoperative complications, and related cost. To deal with selection bias, propensity score matching method was employed at a ratio of 1:1. Meanwhile, a cost-effectiveness analysis was used to evaluate the impact of pharmacist intervention on antibiotic prevention in internal fixation surgery. RESULTS: A total of 537 participants were included in this study. After matching, 236 patients were comparable in each group. During the pharmacist intervention period, less pharmacologic prophylaxis (96.6% vs 100.0%, p = 0.007) and shorter prophylaxis duration (1.60 vs 2.28 days, p < 0.001) were observed. The reasonable rate increased dramatically in usage and dosage (96.6% vs 83.9%, p < 0.001), timing of administration (94.5% vs 78.4%, p < 0.001) and medication duration (64.4% vs 37.7%, p < 0.001). In addition, pharmacist intervention yielded net economic benefits. A remarkable reduction was observed in average length of stay (10.43 vs 11.14 days, p = 0.012), drug cost ($610.57 vs $706.60, p = 0.001) and defined daily doses (2.31 vs 3.27, p < 0.001). The cost-effectiveness ratios, divided drug cost savings by cost of pharmacist time, were 28:1 for drug and 2:1 for antibiotics, respectively. CONCLUSION: Pharmacist-driven antibiotic stewardship for orthopedic internal fixation patients improved compliance with peri-procedure antibiotic prophylaxis, and reduced the cost and utilization of antibiotics. This helped to bring significant clinical and economic benefits.

Optimal dietary standardized ileal digestible lysine level for pigs during the grower, early and late finisher periods.

BACKGROUND: Lysine (Lys) is the first limiting amino acid for pigs fed corn-soybean meal diets. Three experiments were conducted to estimate the optimal standardized ileal digestible (SID) Lys requirement for growing (Exp. 1), early finishing (Exp. 2), and late finishing (Exp. 3) pigs under commercial conditions. RESULTS AND CONCLUSIONS: In Exp. 1, a total of 650 growing pigs (32.21 ± 0.33 kg bodyweight), were allocated to 5 dietary treatments supplemented with 0.75, 0.85, 0.94, 1.03, and 1.13% SID Lys. Each treatment had 5 replicate pens with 26 pigs per pen. The lowest feed to gain ratio (F:G) was obtained by pigs fed the 1.03% Lys diet and F:G showed both a linear and a quadratic response with increasing Lys (P < 0.05). Based on broken-line and quadratic analysis models, dietary SID Lys levels for the minimum F:G were 0.94%. In Exp. 2, 650 finishing pigs (57.24 ± 2.00 kg bodyweight) were allotted to 5 dietary treatments providing SID Lys of 0.63, 0.71, 0.79, 0.87, and 0.95%. Each treatment had 5 replicates, 26 pigs per replication. The highest final bodyweight was achieved by 0.79% Lys while the highest average daily gain (ADG) and average daily feed intake (ADFI) was achieved by pigs consuming the 0.87% Lys diet (P < 0.05). Additionally, the lowest F:G was obtained by pigs fed the 0.79 and 0.87% Lys diet (P < 0.05). Based on broken-line and quadratic analysis models, the optimum Lys was 0.81 and 0.82% for ADG and F:G, respectively. In Exp. 3, 600 late finishing pigs (92.22 ± 2.41 kg bodyweight), were divided into 5 treatments providing Lys levels of 0.53, 0.60, 0.66, 0.73, and 0.79%. Each treatment had 5 replicates, 24 pigs per replication. Results showed that final bodyweight, ADG, ADFI, and F:G was not affected by increasing dietary Lys level, suggesting that the lowest SID Lys (0.53%) was sufficient for this group of pigs. Taken together, the SID Lys requirement for pigs from 30 to 60 kg, 60 to 90 kg, 90 to 120 kg was 0.94%, 0.81 to 0.82, and 0.53%, respectively, depending on the response criteria with performance maximized.

CircRIC8B regulates the lipid metabolism of chronic lymphocytic leukemia through miR199b-5p/LPL axis.

OBJECTIVE: Circular RNAs (circRNAs) play a critical role in the modulation of tumor metabolism. However, the expression patterns and metabolic function of circRNAs in chronic lymphocytic leukemia (CLL) remain largely unknown. This study aimed to elucidate the role of circRNAs in the lipid metabolism of CLL. METHODS: The expression and metabolic patterns of circRNAs in a cohort of 53 patients with CLL were investigated using whole transcriptome sequencing. Cell viability, liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, lipid analysis, Nile red staining as well as triglyceride (TG) assay were used to evaluate the biological function of circRIC8B in CLL. The regulatory mechanisms of circRIC8B/miR-199b-5p/lipoprotein lipase (LPL) axis were explored by luciferase assay, RNA immunoprecipitation (RIP), qRT-PCR, and fluorescence in situ hybridization (FISH). CCK-8 and flow cytometry were used to verify the inhibition role of cholesterol absorption inhibitor, ezetimibe, in CLL cells. RESULTS: Increased circRIC8B expression was positively correlated with advanced progression and poor prognosis. Knockdown of circRIC8B significantly suppressed the proliferation and lipid accumulation of CLL cells. In contrast, the upregulation of circRIC8B exerted opposite effects. Mechanistically, circRIC8B acted as a sponge of miR-199b-5p and prevented it from decreasing the level of LPL mRNA, and this promotes lipid metabolism alteration and facilitates the progression of CLL. What's more, ezetimibe suppressed the expression of LPL mRNA and inhibited the growth of CLL cells. CONCLUSIONS: In this study, the expressional and metabolic patterns of circRNAs in CLL was illustrated for the 1st time. Our findings revealed that circRIC8B regulates the lipid metabolism abnormalities in and development of CLL through the miR-199b-5p/LPL axis. CircRIC8B may serve as a promising prognostic marker and therapeutic target, which enhances the sensitivity to ezetimibe in CLL.

Exploring the significance of PAK1 through chromosome conformation signatures in ibrutinib-resistant chronic lymphocytic leukaemia.

Ibrutinib exerts promising anticancer effects in chronic lymphocytic leukaemia (CLL). However, acquired resistance occurs during treatment, necessitating the exploration of underlying mechanisms. Although three-dimensional genome organization has been identified as a major player in the development and progression of cancer, including drug resistance, little is known regarding its role in CLL. Therefore, we investigated the molecular mechanisms underlying ibrutinib resistance through multi-omics analysis, including high-throughput chromosome conformation capture (Hi-C) technology. We demonstrated that the therapeutic response to ibrutinib is associated with the expression of p21-activated kinase 1 (PAK1). PAK1, which was up-regulated in CLL and associated with patients' survival, was involved in cell proliferation, glycolysis and oxidative phosphorylation. Furthermore, the PAK1 inhibitor IPA-3 exerted an anti-tumour effect and its combination with ibrutinib exhibited a synergistic effect in ibrutinib-sensitive and -resistant cells. These findings suggest the oncogenic role of PAK1 in CLL progression and drug resistance, highlighting PAK1 as a potential diagnostic marker and therapeutic target in CLL including ibrutinib-resistant CLL.

Single-cell profiling-guided combination therapy of c-Fos and histone deacetylase inhibitors in diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Histone deacetylase inhibitors (HDACis) have been widely applied in multiple tumours, but the expected efficacy was not observed in DLBCL. Therefore, this study is aimed to explore superior HDACis and optimise a relative combinational therapeutic strategy. METHODS: The antitumour effects of the drug were evaluated by Cell Counting Kit-8 (CCK-8) assay and apoptosis analysis. Single-cell RNA sequencing (scRNA-Seq) was used to analyse the intratumoural heterogeneity of DLBCL cells. Whole-exome sequencing and RNA sequencing were performed to analyse the genetic and transcriptional features. Western blotting, qRT-PCR, protein array, immunohistochemistry, and chromatin immunoprecipitation assays were applied to explore the involved pathways. The antitumour effects of the compounds were assessed using subcutaneous xenograft tumour models. RESULTS: LAQ824 was screened and confirmed to kill DLBCL cells effectively. Using scRNA-Seq, we characterised the heterogeneity of DLBCL cells under different drug pressures, and c-Fos was identified as a critical factor in the survival of residual tumour cells. Moreover, we demonstrated that combinatorial treatment with LAQ824 and a c-Fos inhibitor more potently inhibited tumour cells both in vitro and in vivo. CONCLUSION: Altogether, we found an HDACi, LAQ824, with high efficacy in DLBCL and provided a promising HDACi-based combination therapy strategy.

Functional Evaluation of KEL as an Oncogenic Gene in the Progression of Acute Erythroleukemia.

Acute erythroleukemia (AEL) is an infrequent subtype of acute myeloid leukemia (AML) with worse prognosis. Though the last decade has seen major advances in the novel features and genomic landscape in AEL, there is still a lack of specific therapeutic targets and effective treatment approaches for this disease. Here, we found a novel oncogene KEL that specifically and aberrantly expressed in patients with AEL. In this study, we demonstrated that KEL promoted cell proliferation and the downregulation of KEL reversed drug resistance in AEL cells to JQ1. Our findings suggested that KEL contributed to gain of H3K27 acetylation and promoted erythroid differentiation induced by GATA1. Additionally, GATA1 and TAL1 as cotranscription factors (TFs) modulated the expression of KEL. Maintaining cell viability and differentiation, KEL also played parts in the immune evasion of tumor cells. Our work expands the current knowledge regarding molecular mechanisms involved in cancer onset and progression, offering promising therapeutic target to broaden the treatment options.

Body mass index and pharmacodynamics of target-controlled infusion of propofol: A prospective non-randomized controlled study.

WHAT IS KNOWN AND OBJECTIVE: In our preliminary study, there were large individual variations at sedation levels during propofol target-controlled infusion (TCI). The present study aimed to assess the effects of body mass index (BMI) on the pharmacodynamic index of propofol TCI. METHODS: This prospective, non-randomized controlled trial evaluated 175 female patients undergoing breast lumpectomy. Anesthesia was induced with propofol using the TCI system embedded Schnider model. The effect compartment concentration was set to 3 µg/ml, and the start time of infusion was recorded. When the target concentration reached 3 µg/ml, the patient could not be awakened (Ramsay sedation score ≥4), and when the Bispectral Index (BIS) was <60, the infusion was discontinued, and the time point was recorded. The observation end-point was set at the Observer's Assessment of Alertness/Sedation (OAA/S) score of <4. The correlation between the BMI and the pharmacodynamic index of propofol was evaluated. RESULTS AND DISCUSSION: Propofol induction time was significantly correlated with the BMI (p < 0.001). The induction time of the underweight subjects was 10.14 ± 2.19 min, which was remarkably higher than that of normal weight (6.48 ± 3.44 min) and overweight (4.75 ± 2.53 min) individuals (p < 0.001). There were still significant differences after multivariable-adjusted regressions (p < 0.001). There were no significant differences in recovery time and sedative effect indicators, such as Ramsay score, BIS value, and effect compartment concentration, between the three groups (p > 0.05 for all). WHAT IS NEW AND CONCLUSION: These results suggest that the BMI is one of the critical factors affecting the pharmacodynamic index of propofol TCI, and the induction time decreased progressively with increasing BMI. The Schnider model might underpredict doses of propofol for underweight individuals.

Comparison of expression profiles between undifferentiated and differentiated porcine IPEC-J2 cells.

BACKGROUND: The intestinal porcine enterocyte cell line (IPEC-J2) is a well-established model to study porcine intestinal physiology. IPEC-J2 cells undergo spontaneous differentiation during culture while changes in expression patterns of differentiated IPEC-J2 remain unclear. Therefore, this study was aimed to investigate the expression profiles of IPEC-J2 cells at the transcriptional level. Differentially expressed genes (DEGs), enriched pathways and potential key genes were identified. Alkaline phosphatase (AKP) and percentages of apoptotic cells were also measured. RESULTS: Overall, a total of 988 DEGs were identified, including 704 up-regulated and 284 down-regulated genes. GO analysis revealed that epithelial cell differentiation, apoptotic signaling pathway, regulation of cytokine production and immune system process, regulation of cell death and proliferation, cell junction complexes, and kinase binding were enriched significantly. Consistently, KEGG, REACTOME, and CORUM analysis indicated that cytokine responses modulation may be involved in IPEC-J2 differentiation. Moreover, AKP activity, a recognized marker of enterocyte differentiation, was significantly increased in IPEC-J2 after 14 days of culture. Meanwhile, annexin V-FITC/PI assay demonstrated a remarkable increase in apoptotic cells after 14 days of culture. Additionally, 10 hub genes were extracted, and STAT1, AKT3, and VEGFA were speculated to play roles in IPEC-J2 differentiation. CONCLUSIONS: These findings may contribute to the molecular characterization of IPEC-J2, and may progress the understanding of cellular differentiation of swine intestinal epithelium.

CircRNA May Not Be "Circular".

Circular RNA (circRNA) is a novel regulatory non-coding RNA and participates in diverse physiological and pathological processes. However, the structures and molecular mechanisms of circRNAs remain unclear. In this study, taking advantage of openly databases and bioinformatics analysis, we observed lots of internal complementary base-pairing sequences (ICBPS) existed in plenty of circRNAs, especially in extremely long circRNAs (el-circRNAs, > 5,000 nt). The result indicated that circRNA may not be a simple circular structure. In addition, we put forward the hypothesis of "open-close effect" in the transition for specific circRNA from normal state to morbid state. Taken together, our results not only expand the knowledge of circRNAs, but also highlight the potential molecular mechanism of circRNAs.

Diagnostic value and clinical significance of circulating miR-650 and CA211 in detecting of gastric carcinoma.

The present study determined the levels of plasma biomarkers in patients with gastric carcinoma (GC) and investigated their clinical significance and diagnostic value. Between April 2014 and December 2018, 90 patients with GC, 90 patients with precancerous lesions (Pre) and 45 healthy controls (NC) were recruited from the Affiliated Liutie Central Hospital of Guangxi Medical University. Five markers were measured: microRNA-650 (miRNA-650; using reverse transcription-quantitative polymerase chain reaction), and carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125, CA211 and CA50 using electrochemiluminescence. Circulating markers were all upregulated in patients with GC (P<0.05), and CA211 and CA50 were significantly increased in patients with Pre. The miRNA-650 and CA211 had an area under the curve (AUC) of 0.700 (moderate) and 0.866 (high), respectively, in the diagnosis of GC. Differentiation of GC from Pre yielded an AUC of 0.665 (low) and 0.708 (moderate), respectively. The combination model of miRNA-650 and CA211 showed an appropriate value of AUC (0.887) to discriminate the GC patients from the healthy subjects with a sensitivity and specificity of 82.5 and 97.7%. Additionally, differentiating GC from Pre yielded an AUC of 0.767 with a sensitivity of 57.1% and a specificity of 95%, respectively. In terms of clinicopathological features, the expression of miRNA-650 and CA211 in plasma was not associated with the patients' age, sex, Tumor-Node-Metastasis stage, or histological type. In conclusion, plasma miRNA-650 and CA211 is a promising and powerful non-invasive marker for the detection of GC.

Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia.

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 RNAs in leukemia.

In pace with the development of gene sequencing technology and transcriptome research, it has been found that 70 to 90% of the human genome is transcribed into RNAs, while only 2% of RNAs encode proteins. This implies that non-coding RNAs (ncRNAs) may exert vital biological functions and a full analysis of non-coding transcriptomes is needed. Over the past decade, the advance in high-throughput sequencing and transcriptome profiling has enabled the identification of circular RNAs (circRNAs) involved in many biological processes and the occurrence and development of diseases. Accumulating evidence has revealed that circRNAs may serve as new biomarkers for diagnosis as well as provide promising therapeutic approaches and novel drug screening strategies for leukemia. A comprehensive understanding of circRNAs in leukemia is a prerequisite for the development of clinical translational research. In this review, we will discuss the general information of circRNAs and focus on the current advances in understanding the association between dysregulated circRNAs and leukemia.

Downregulation of circ_0132266 in chronic lymphocytic leukemia promoted cell viability through miR-337-3p/PML axis.

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.