Circular RNA circ_0020123 promotes non-small cell lung cancer progression by sponging miR-590-5p to regulate THBS2.

BACKGROUND: The incidence and death rate of non-small cell lung cancer (NSCLC) in China ranks the first among the malignant tumors. Circular RNA (circRNA) was reported to be involved in the progression of NSCLC. Our study aimed to investigate the underlying mechanism of circ_0020123 in NSCLC progression. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0020123, miR-590-5p and Thrombospondin 2 (THBS2) in NSCLC tissues and cells. Cell proliferation and migration were examined by Cell Counting Kit-8 (CCK-8) assay and Transwell assay, respectively. Flow cytometry assay was used to detect the apoptosis of NSCLC cells. The protein levels of Ki-67, matrix metalloprotein-9 (MMP-9), Cleaved-caspase9 (Cleaved-casp9) and THBS2 were detected by Western blot. The targets of circ_0020123 and miR-590-5p were predicted by starBase 3.0 and TargetScan, and then confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The animal experiment showed the effect of circ_0020123 on tumor growth in vivo. RESULTS: The expression of circ_0020123 was upregulated in NSCLC tissues and cells. Functionally, circ_0020123 downregulation inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. Interestingly, circ_0020123 directly targeted miR-590-5p, and inhibition of miR-590-5p reversed the knockdown effects of circ_0020123 on NSCLC cells. More importantly, THBS2 was a target of miR-590-5p, and THBS2 overexpression reversed the effects of circ_0020123 knockdown on cell proliferation, migration and apoptosis in NSCLC cells. Finally, suppression of circ_0020123 inhibited tumor growth in vivo through miR-590-5p/THBS2 axis. CONCLUSION: Circular RNA circ_0020123 regulated THBS2 by sponging miR-590-5p to promote cell proliferation and migration and inhibit cell apoptosis in NSCLC cells.

The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury.

The mitochondrial calcium uniporter (MCU) transports free Ca(2+) into the mitochondrial matrix, maintaining Ca(2+) homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MCU and mitochondrial fission during the process of ischemia/reperfusion injury. This study constructed a hypoxia reoxygenation model using primary hippocampus neurons to mimic the cerebral ischemia/reperfusion injury and aims to explore the exactly effect of MCU on the mitochondrial fission during the process of ischemia/reperfusion injury and so as the mechanisms. Our results found that the inhibitor of the MCU, Ru360, decreased mitochondrial Ca(2+) concentration, suppressed the expression of mitochondrial fission protein Drp1, MIEF1 and Fis1, and thus improved mitochondrial morphology significantly. Whereas spermine, the agonist of the MCU, had no significant impact compared to the I/R group. This study demonstrated that the MCU regulates the process of mitochondrial fission by controlling the Ca(2+) transport, directly upregulating mitochondrial fission proteins Drp1, Fis1 and indirectly reversing the MIEF1-induced mitochondrial fusion. It also provides new targets for brain protection during ischemia/reperfusion injury.

CircTFF1 Promotes Proliferation, Migration and Invasion of Lung Cancer Cells by Facilitating Methylation of BCL6B Promoter via miR-29c-3p/DNMT3A Axis.

Lung cancer exists as a major risk of cancer-related death worldwide. As a novel circular RNA (circRNA), circTFF1 has not been explored in lung cancer thoroughly. This study aims to probe into the function and mechanism of circTFF1 in lung cancer. RT-qPCR and western blot were used to detect expression of RNAs and proteins. The influence of circTFF1 and BCL6B on cells behavior was explored via CCK-8 assay, colony formation assay, wound healing assay and transwell assay. Methylation of BCL6B was detected via MSP assay. Bioinformatics analysis and mechanism assays were conducted for investigating the interaction among genes. CircTFF1 was found to be upregulated in lung cancer cell lines used in this study. Functional experiments revealed circTFF1 facilitated cell proliferation, migration and invasion. BCL6B was downregulated in lung cancer cell lines used in this study, and the downregulation of BCL6B was mainly mediated by methylation. Additionally, BCL6B exerted suppressive impacts on lung cancer cell line malignant behavior. Moreover, circTFF1 acted as the miR-29c-3p sponge to upregulate DNMT3A, which facilitated the methylation of BCL6B. In all, circTFF1 promoted proliferation, migration and invasion of lung cancer cell lines by facilitating methylation of BCL6B promoter via miR-29c-3p/DNMT3A axis.

Effects of MCU-mediated Ca2+ Homeostasis on Ovarian Cancer Cell SKOV3 Proliferation, Migration and Transformation.

BACKGROUND: Atlas human proteomics database showed MCU as highly expressed in various tumor tissues, especially in ovarian cancer. Rare studies on the role of MCU and its regulation in ovarian cancer have been reported. OBJECTIVE: The objective of this study was to determine role of MCU in ovarian cancer cell SKOV3 proliferation, migration, and transformation, and explore the possible mechanism. METHODS: MCU siRNA on lentiviral particles were stably transfected into SKOV3 cells. CCK-8 assay was performed to analyze cell proliferation. Soft-agar colony formation assay was employed to evaluate tumorigenesis. Western blot and immunohistochemistry analyses were performed to evaluate the expression of MCU, MICU1 and phosphorylate of Akt in the ovarian cancer cell and tissue specimens. Scratch assay was combined with trans-well plates assay to detect the migration ability of cancer cells. The ROS production and Ca2+ expression were also determined. RESULTS: MCU expression was significantly higher in ovarian cancer tissues than normal tissues. MCU silencing decreased SKOV3 cell proliferation, migration, and transformation. ROS production was decreased after MCU silencing, depending on disturbed Ca2+ homeostasis. MICU1 expression has been found to be decreased and phosphorylation of Akt increased when MCU was silenced. CONCLUSION: Down-regulation of MCU inhibited SKOV3 cell proliferation, migration, and transformation via disturbing Ca2+ homeostasis and decreasing ROS production. MICU1 and phosphorylation of Akt are associated with MCU-mediated ovarian cancer malignancy.

Characterization of glucose metabolism in breast cancer to guide clinical therapy.

Background: Breast cancer (BRCA) ranks as a leading cause of cancer death in women worldwide. Glucose metabolism is a noticeable characteristic of the occurrence of malignant tumors. In this study, we aimed to construct a novel glycometabolism-related gene (GRG) signature to predict overall survival (OS), immune infiltration and therapeutic response in BRCA patients. Materials and methods: The mRNA sequencing and corresponding clinical data of BRCA patients were obtained from public cohorts. Lasso regression was applied to establish a GRG signature. The immune infiltration was evaluated with the ESTIMATE and CIBERSORT algorithms. The drug sensitivity was estimated using the value of IC50, and further forecasted the therapeutic response of each patient. The candidate target was selected in Cytoscape. A nomogram was constructed via the R package of "rms". Results: We constructed a six-GRG signature based on CACNA1H, CHPF, IRS2, NT5E, SDC1 and ATP6AP1, and the high-risk patients were correlated with poorer OS (P = 2.515 × 10-7). M2 macrophage infiltration was considerably superior in high-risk patients, and CD8+ T cell infiltration was significantly higher in low-risk patients. Additionally, the high-risk group was more sensitive to Lapatinib. Fortunately, SDC1 was recognized as candidate target and patients had a better OS in the low-SDC1 group. A nomogram integrating the GRG signature was developed, and calibration curves were consistent between the actual and predicted OS. Conclusions: We identified a novel GRG signature complementing the present understanding of the targeted therapy and immune biomarker in breast cancer. The GRGs may provide fresh insights for individualized management of BRCA patients.

Uniportal video-assisted versus open pneumonectomy: a propensity score-matched comparative analysis with short-term outcomes.

OBJECTIVES: Uniportal (U-VATS) pneumonectomy in lung cancer patients remains disputed in terms of oncological outcomes, and has not been compared to open approaches previously. We evaluated U-VATS versus open pneumonectomy at a high-volume centre. METHODS: Patients undergoing pneumonectomy for lung cancer between 2014 and 2018 were retrospectively reviewed and divided into two groups based on surgical approach. Propensity-score matching was performed (1:1), and intention-to-treat analysis applied. Overall survival, operative time, intraoperative blood loss, hospital-stay and readmission, pain, time to adjuvant therapy, morbidity and mortality were tested. Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc. NC) RESULTS: 341 patients underwent pneumonectomy; 23 patients with small-cell lung cancer were excluded, thus 318 patients were submitted to surgery by either U-VATS (n = 54) or open (n = 264). After matching, 52 patients were selected from each group. Five patients (9.2%) in the uniportal group required conversion. There was no significant difference in intraoperative outcomes, complication rates, readmission rates or mortality. The U-VATS group experienced significantly shorter hospital stay (mean ± SD; 6.7 ± 2.7 vs 9.1 ± 2.3 days, p < 0.001) and reported less pain postoperatively (p < 0.0001). Adjuvant chemotherapy was initiated sooner after U-VATS (38.1 ± 8.4 vs 50.8 ± 11.5 days, p < 0.0001). Overall survival appeared to be superior in U-VATS when pathology stage was aligned (p = 0.001). CONCLUSIONS: Uniportal VATS is a safe and effective alternative approach to open surgery for pneumonectomy in lung cancer. Complications and oncologic outcomes were comparatively similar. U-VATS showed lower postoperative pain, shorter hospital stay and superior overall survival. The study is a preliminary analysis.