GAS6-AS1 Overexpression Increases GIMAP6 Expression and Inhibits Lung Adenocarcinoma Progression by Sponging miR-24-3p.

GAS6 antisense RNA 1 (GAS6-AS1) is a long non-coding RNA involved in hepatocellular carcinoma and gastric cancer. However, the functional role of GAS6-AS1 in lung adenocarcinoma (LUAD) remains unclear. In the present study, qRT-PCR was used to measure the levels of GAS6-AS1, GIMAP6 and miR-24-3p expression in LUAD samples and cell lines. CCK-8 and colony formation assays were used to determine cell proliferation. Cell migration and invasion were evaluated using wound healing and transwell assays, respectively. The potential interactions between molecules were assessed using RNA immunoprecipitation and luciferase reporter assays. Western blot analysis was used to quantify protein expression. The anti-tumor effect of over-expressed GAS6-AS1 on LUAD was also examined in vivo in xenograft tumor experiments. The expression of GAS6-AS1 was notably downregulated in LUAD samples and cell lines and associated with a poor prognosis. GAS6-AS1 overexpression inhibited the migration and invasion of A549 and H1650 cells. Down-expressed GAS6-AS1 acted as a sponge for miR-24-3p and down-regulated the expression of its target, GTPase IMAP Family Member 6. These findings suggested that GAS6-AS1 might represent a potential diagnostic biomarker for LUAD.

Overexpression of hsa_circ_0008274 inhibited the progression of lung adenocarcinoma by regulating HMGA2 via sponging miR-578.

BACKGROUND: Circular RNAs (circRNAs) had been identified as a non-coding RNA associated with many types of cancer in recent years. However, the involvement of hsa_circ_0008274 in lung adenocarcinoma (LUAD) has not been explored. The aim of our research is to explore the biological mechanism and function of hsa_circ_0008274 in LUAD. METHODS: The hsa_circ_0008274, miR-578, and high mobility group AT-Hook 2 (HMGA2) mRNA expression levels were detected via qRT-PCR. Cell Counting Kit-8 (CCK-8) Transwell assay and wound healing assay were performed to measure the cell proliferation, invasion, and migration ability. Luciferase reporter and Western blotting experiments were performed to characterize the competing endogenous RNA (ceRNA) mechanism of hsa_circ_0008274. RESULTS: Our findings determined that the expression of hsa_circ_0008274 in LUAD was significantly decreased. Cell experiments showed that overexpressed hsa_circ_0008274 could reduce the proliferation and invasion ability of LUAD cells. Moreover, miRNA-578 could identify as a miRNA sponge of hsa_circ_0008274. Overexpressed hsa_circ_0008274 reduced the proliferation and invasion of LUAD cells caused by miR-578 mimics. Increasing the expression of miR-578 can aggravate the proliferation and invasion of LUAD cells and block the inhibition of proliferation and invasion of LUAD cells mediated by overexpressed hsa_circ_0008274. Subsequent data indicate that HMGA2 of the tumor-promoting gene is the target gene of miR-578. The upregulation of HMGA2 partially reversed the tumor inhibitory effect of LUAD cells induced by overexpressed hsa_circ_0008274 or miR-578 mimics. CONCLUSIONS: In summary, our data show that the overexpression of hsa_circ_0008274 repressed the proliferation and invasion of LUAD through downregulating miR-578 and activating HMGA2.

Assessment of safety margin after microwave ablation of stage I NSCLC with three-dimensional reconstruction technique using CT imaging.

OBJECTIVE: To assess the ablative margin of microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) using a three-dimensional (3D) reconstruction technique. MATERIALS AND METHODS: We retrospectively analyzed 36 patients with stage I NSCLC lesions undergoing MWA and analyzed the relationship between minimal ablative margin and the local tumor progression (LTP) interval, the distant metastasis interval and disease-free survival (DFS). The minimal ablative margin was measured using the fusion of 3D computed tomography reconstruction technique. RESULTS: Univariate and multivariate analyses indicated that tumor size (hazard ratio [HR] = 1.91, P < 0.01; HR = 2.41, P = 0.01) and minimal ablative margin (HR = 0.13, P < 0.01; HR = 0.11, P < 0.01) were independent prognostic factors for the LTP interval. Tumor size (HR = 1.96, P < 0.01; HR = 2.35, P < 0.01) and minimal ablative margin (HR = 0.17, P < 0.01; HR = 0.13, P < 0.01) were independent prognostic factors for DFS by univariate and multivariate analyses. In the group with a minimal ablative margin < 5 mm, the 1-year and 2-year local progression-free rates were 35.7% and 15.9%, respectively. The 1-year and 2-year distant metastasis-free rates were 75.6% and 75.6%, respectively; the 1-year and 2-year disease-free survival rates were 16.7% and 11.1%, respectively. In the group with a minimal ablative margin ≥ 5 mm, the 1-year and 2-year local progression-free rates were 88.9% and 69.4%, respectively. The 1-year and 2-year distant metastasis-free rates were 94.4% and 86.6%, respectively; the 1-year and 2-year disease-free survival rates were 88.9% and 63.7%, respectively. The feasibility of 3D quantitative analysis of the ablative margins after MWA for NSCLC has been validated. CONCLUSIONS: The minimal ablative margin is an independent factor of NSCLC relapse after MWA, and the fusion of 3D reconstruction technique can feasibly assess the minimal ablative margin.

Serum homocysteine level is an independent predictor for hemorrhagic transformation within 24 h of intravenous thrombolysis in acute ischemic stroke.

The study aimed to investigate the role of serum homocysteine in hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 h of intravenous (IV) recombinanttissueplasminogenactivator(rt-PA) in acute ischemic stroke (AIS) patients. 236 consecutive AIS patients (169 men, median 65 years old) who underwent to IV rt-PA within 4.5 h of symptom onset were retrospectively recruited and analyzed. The serum homocysteine levels ranged from 4.45 to 67.71 (median 12.05) µmol/L. HT was observed in 28 (11.9%) patients, including 7 (3.0%) sICH patients within 24 h of IV rt-PA. Multiple parameters were compared between HT and non-HT patients as well as sICH and non-sICH patients. The serum homocysteine levels were higher in patients with HT than in those without HT (13.00 vs. 11.70 µmol/L, P = 0.025) and an independent association between serum homocysteine level and HT within 24 h of IV rt-PA was identified via multivariable logistic regression analysis (odds ratio [OR] = 1.103, 95% confidence interval [CI] = 1.021-1.191, P = 0.013). Moreover, serum homocysteine levels were also significantly higher in patients with sICH than in those without sICH (15.19 vs. 11.73 µmol/L, P = 0.005).Our study suggests that serum homocysteine level is an independent predictor for HT within 24 h of IV rt-PA in AIS patients.

Preferentially Disrupted Core Hubs Within the Default-Mode Network in Patients With End-Stage Renal Disease: A Resting-State Functional Magnetic Resonance Imaging Study.

Neuroimaging evidence implies that cognitive impairment in patients with end-stage renal disease (ESRD) is related to the disruption of the default-mode network (DMN). The DMN can be divided into three functionally independent subsystems, which include the cortical hub subsystem [consisting of the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC)], the dorsal medial prefrontal cortex (dMPFC) subsystem, and the medial temporal lobe (MTL) subsystem. However, it is unknown how the functional connectivity (FC) in DMN subsystems is differentially impaired in ESRD. This prospective study was carried out at the Affiliated Hospital of Qingdao University, China, between August 2018 and July 2020. Thirty-two ESRD patients and forty-five healthy controls (HCs) were recruited for this study and received resting-state functional magnetic resonance imaging (rs-fMRI) scanning, and FCs on predefined regions of interest (ROIs) were individually calculated in three DMN subsystems using both ROI- and seed-based FC analyses to examine FC alterations within and between DMN subsystems. The two-sample t-test was used for the comparisons between groups. We also tested the associations between FC changes and clinical information using Pearson's correlation analysis. The results demonstrated that ESRD patients, compared with HCs, exhibit reduced FC specifically within the cortical hubs and between the DMN hubs and two subsystems (the dMPFC and MTL subsystems). Moreover, the FC values between the aMPFC and PCC were positively correlated with creatinine and urea levels in the ESRD patients. Our results suggest that the cortical hubs (PCC and aMPFC) are preferentially disrupted and that other subsystems may be progressively damaged to a certain degree as the disease develops.