A Dosimetric Comparative Study of Carbon-Ion Radiotherapy Versus X-ray Volumetric Modulated Arc Therapy for Stage III Non-Small-Cell Lung Cancer.

BACKGROUND: Compared to photon beam, carbon-ion radiotherapy (CIRT) has both physical and biological advantages. AIM: To examine whether two-dimensional (2D) CIRT is dosimetrically superior to photon beam volume-modulated arc therapy (VMAT) in protecting the normal tissues for stage III non-small-cell lung cancer (NSCLC). SUBJECTS AND METHODS: A retrospective study was conducted. Thirteen patients with stage III NSCLC treated in our center with curative CIRT and a sham photon beam VMAT treatment planning with the same normal tissue dose constraints were included for analysis. Target dose distributions and the homogeneity index (HI) within the planning target volumes were compared. RESULTS: Both CIRT and VMAT plans have good tumor coverage with no significant differences in D98, D95, and D50 of Planning target volume 1 (PTV1) between the two plans. The HIs between the two plans are similar. The HI of PTV2 is superior in the CIRT plan (CIRT vs. VMAT: 0.08 vs. 0.16, P < 0.05). In general, CIRT results in a lower dose of the organ-at-risk (OAR) than the photon plans. The V5, V10, V20, V30, V40, and Dmean of the contralateral lung in the CIRT plan are significantly lower than that of the photon VMAT. For the ipsilateral lung, the V5 of CIRT is significantly lower. The CIRT also had significantly lower spinal cord Dmax, esophageal Dmean and V50, V10 and V30 of bone, and V50 of the trachea and bronchial tree. CONCLUSIONS: Compared with photon VMAT, 2D-CIRT using the passive beam scanning technique significantly reduces the radiation dose to the OARs in curative radiotherapy of stage III NSCLC, suggesting a better protection of the normal tissues.

The expression of annexin-A1 in esophageal squamous cell carcinoma and its association with the biological behavior of the primary human esophageal squamous carcinoma cell line.

This study aimed to observe the differential expression of Annexin-A1 in esophageal squamous cell carcinoma (ESCC) and explored the effect of small interfering ribonucleic acid (RNAi)-Annexin-A1 on the biological behavior of CE81T-0 cells. An immunohistochemical approach was used to detect the expression of Annexin-A1 in 86 pairs of ESCC samples. Quantitative reverse transcription polymerase chain reaction was used to detect the expression of Annexin-A1 in CE81T-0 and CE81T-4 cells, and the expression of Annexin-A1 in CE81T-0 cells was knocked out by RNAi. A methyl-thiazolyl-tetrazolium assay was used to observe the effect of Annexin-A1 on cell proliferation, and flow cytometry was conducted to analyze its effect on cell cycles and apoptosis. A scratch assay and a Transwell chamber were used to detect changes in cell migration and invasion. From the results, compared with the Annexin-A1 expression rate of 59.3% in para-carcinoma tissues, the expression of Annexin-A1 in cancer was reduced to only 32.6% in ESCC cells. Annexin-A1 was strongly expressed in highly differentiated ESCC cells without lymphatic metastasis and highly expressed in the CE81T-0 cell group with low metastasis. Annexin-A1 gene silencing promoted cell proliferation and inhibited apoptosis, blocked cells in the S-phase, and increased cell migration, leading to an increase in the number of invaded cells. Above all, Annexin-A1 could reflect the differentiation degree and lymph node metastasis of ESCC cells to some extent and was involved in the invasion, metastasis, proliferation, and other biological behaviors of ESCC cells, indicating an experimental basis for Annexin-A1 as a molecular marker in the early diagnosis of ESCC and the prediction of cell metastasis, invasion, and differentiation degree.

Late-Night Overeating and All-Cause and Cardiovascular Disease Mortality in Adults Aged ≥ 50: A Cohort Study.

BACKGROUND: Late-night overeating (LNOE) is closely associated with many health risk factors, but whether LNOE can increase the risk of death remains unknown. Thus, the prospective cohort study aimed to investigate the relationship between LNOE and mortality using data from the National Health and Nutrition Examination Survey. METHODS: 11,893 participants aged 50 years and older were included in the study. Dietary information was obtained through 24-h dietary recall interviews. Cox regression, subgroup, sensitivity, and restricted cubic spline analyses were used to assess the association between LNOE and mortality. RESULTS: During a median follow-up of 8.3 years, 2,498 deaths occurred. After adjusting for major confounders, compared to the non-late-night eating (NLNE) group, the LNOE group was associated with higher risks of all-cause (HR = 1.47, 95% CI = 1.06-2.04) and cardiovascular disease (CVD) mortality (HR = 2.02, 95% CI = 1.13-3.60). No significant association was found between late-night eating (LNE) and mortality. Subgroup analyses showed that the LNOE group had a greater risk of all-cause and CVD mortality in participants older than 70 years, with alcohol consumption and hypertension and demonstrated an increased risk of all-cause mortality in males and higher CVD mortality in females. CONCLUSION: The habit of LNOE was an independent risk factor for all-cause and CVD mortality in US adults aged 50 years and older, which was also influenced by age, sex, alcohol consumption, and hypertension.

Correlation of serum levels of HIF-1α, SMAD3, and HDAC3 with the disease severity in stroke patients.

OBJECTIVE: Explore serum levels of hypoxia-inducible factor-1α (HIF-1α), signal transduction molecule 3 (SMAD3), and histone deacetylase (HDAC) and their correlation with the severity of the condition of stroke patients. PATIENTS AND METHODS: Clinical records of 93 stroke patients and 93 healthy individuals were retrospectively analyzed. Serum levels of HIF-1α, SMAD3, and HDAC3 in patients with different disease degrees and lesion areas were compared between the two groups. Correlation between serum levels of HIF-1α, SMAD3, and HDAC3 and the severity and lesion area of the observation group were analyzed. RESULTS: Serum levels of HIF-1α, SMAD3, and HDAC3 in the observation group were higher than those in the control group (p<0.05). Serum levels of HIF-1α, SMAD3, and HDAC3 in patients with moderate and severe disease were significantly higher than those in patients with mild disease and were the highest in patients with severe disease (p<0.05). Serum levels of HIF-1α, SMAD3, and HDAC3 in patients with moderate and large areas of cerebral infarction were significantly higher than those in patients with small areas of cerebral infarction and the highest in patients with large areas of cerebral infarction (p<0.05). Spearman correlation analysis showed that serum levels of HIF-1α, SMAD3, and HDAC3 significantly positively correlated with the severity of stroke and lesion area (p<0.05). CONCLUSIONS: Serum levels of HIF-1α, SMAD3, and HDAC3 in stroke patients are highly expressed, and the increase positively correlates with the severity of the disease and the area of the lesion.

An approach combining bioinformatics and machine learning to identify eight autophagy-related biomarkers and construct molecular mechanisms underlying COVID-19 and major depressive disorders.

OBJECTIVE: A lack of objective biomarkers is preventing the screening and diagnosis of COVID-19 combined with major depression disorder (COVID-19-MDD). The purpose of this study was to identify diagnostic biomarkers and gene regulatory mechanisms associated with autophagy; a crucial process significantly involved in the pathogenesis of COVID-19-MDD. MATERIALS AND METHODS: In this study, differentially expressed genes (DEGs) were screened using GSE98793 from the GEO2R analysis (GEO) database, and intersected with the COVID-19-related gene (CRGs) and autophagy-related genes (ARGs) to obtain common genes involved in. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these common genes were performed. Subsequently, the transcription factor (TF)-gene regulatory network and comorbidity network were constructed. In addition, 10 drug candidates were screened using the DSigDB database. To identify diagnostic markers, we used LASSO regression. RESULTS: In total, 13 common genes were screened, which were primarily enriched in lysosomes, endoplasmic reticulum membranes, and other endomembrane systems also associated with autophagy. Additionally, these genes were involved in neurological cell signaling and have a functional role in pathways related to vascular endothelial growth factor, tyrosine kinase, autophagy, inflammation, immunity, and carcinogenesis. Tumors and psychiatric disorders were the most highly linked diseases to COVID-19. Finally, ten drug candidates and eight diagnostic markers (STX17, NRG1, RRAGD, XPO1, HERC1, HSP90AB1, EPHB2, and S1PR3) were screened. CONCLUSIONS: This is the first study to screen eight diagnostic markers and construct a gene regulatory network for COVID-19-MDD from the perspective of autophagy. The findings of our study provide novel insights into the diagnosis and treatment of COVID-19-MDD.

Retraction Note: METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2.

The article "METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2, by Q.-Z. Meng, C.-H. Cong, X.-J. Li, F. Zhu, X. Zhao, F.-W. Chen, published in Eur Rev Med Pharmacol Sci 2020; 24 (8): 4328-4336-DOI: 10.26355/eurrev_202004_21014-PMID: 32373970" has been retracted by the authors. After publication, several issues were raised on PubPeer about the reliability of the published results. The same authors stated that the study was not performed in accordance with the standard procedures required. In particular, Figure 1 also presents some concerns as it does not reflect the experimental data reported in the study. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21014.

Causal roles of daytime sleepiness in cardiometabolic diseases and osteoporosis.

OBJECTIVE: Daytime sleepiness has some association with cardiometabolic diseases and osteoporosis, but it is unknown whether their relationship is causal. This two-sample Mendelian randomization (MR) study aims to explore their causal relationship. MATERIALS AND METHODS: We included the largest genome-wide association studies (GWASs) associated with daytime sleepiness, cardiometabolic diseases and osteoporosis. 34 single nucleotide polymorphisms (SNPs) were used as the instrumental variables of daytime sleepiness. RESULTS: Genetic predisposition to excessive daytime sleepiness was strongly associated with increased risk of coronary artery disease (beta-estimate: 0.610, 95% confidence interval [CI]: 0.128 to 1.093, standard error [SE]: 0.246, p-value=0.013) and may increase the incidence of type 2 diabetes (beta-estimate: 0.614, 95% CI: 0.009 to 1.219, SE: 0.309, p-value=0.047). We found no causal influence of daytime sleepiness on heart failure, atrial fibrillation, cerebral ischemia, intracerebral hemorrhage, forearm bone mineral density (FA-BMD), femoral neck BMD (FN-BMD), and lumbar spine BMD (LS-BMD). CONCLUSIONS: This study suggested that excessive daytime sleepiness was causally associated with increased risk of coronary artery disease, which may benefit to prevent this disease.

Establishment of esophageal squamous carcinoma cell lines with different invasive metastatic potential and differential gene screening.

The present study aimed to establish esophageal squamous carcinoma cell (ESCC) sublines with different invasive and metastatic potentials. Gene microarrays were used for differential gene screening with the establishment of ESCC invasive metastatic gene expression profiles. Some differential gene expressions were validated. Parent line Eca109-T0 was screened in a Transwell chamber to establish Eca109-T4 with high invasion and metastasis. The migrative and proliferative capacities of ESCCs were compared. The Eca109-T0 and Eca109-T4 cell lines were taken as the research objects and were hybridized with gene chips to obtain cell sublines for the screening of differential genes of ESCCs with varying invasive and metastatic potentials. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) clustering analyses were conducted. Some differential genes (HSP90AA1, ANXA1, YWHAB, CXCR7, SDC2, and TNFRSF10D messenger ribonucleic acid) were validated by qualitative real-time polymerase chain reaction and Western blot analysis. As a result, some Eca109-T4 ESCC sublines with high invasive and metastatic potential were screened in a Transwell chamber. The gene chip analysis screened out 326 differential genes, of which 123 were upregulated and 203 were downregulated by Eca109-T4. The GO cluster analysis indicated that the genes were in the cytoplasm, nucleus, and cytosol. The molecular functions of these genes involved the binding of proteins and metal ions and participation in biological processes, including cell signal transduction, transcription, and apoptosis. The KEGG clustering showed that these genes were mainly involved in signaling pathways, such as actin cytoskeleton regulation, the mitogen-activated protein kinase pathway, and the cancer pathway. The validation results were basically consistent with the gene microarray screening results. In Eca109-T4 and CE81T-4, HSP90AA1, YWHAB, and CXCR7 were highly expressed, while the expression of ANXA1 was low. In conclusion esophageal squamous carcinoma cell models with different invasive and metastatic potentials were established. The establishment of differential gene expression profiles for invasion and metastasis together with a bioinformatics analysis provided rich information for studies related to ESCC invasion and metastasis. HSP90α, 14-3-3ß, and CXCR7 were highly expressed in ESCCs with high invasion and metastasis, while Annexin A1 was highly expressed in ESCCs with low metastasis.

Genome-wide association studies for growth-related traits in a crossbreed pig population.

Growth-related traits are important economic traits in the pig industry that directly influence pork production efficiency. To detect quantitative trait loci and candidate genes affecting growth traits, genome-wide association studies were performed for backfat thickness (BF) and loin muscle depth (LMD) in 370 Chuying-black pigs using Illumina PorcineSNP50 BeadChip array. We totally identified 14 BF-associated SNPs, which included 11 genome-wide SNPs (P < 1.39E-06) and 3 chromosome-wide suggestive SNPs (P < 2.79E-05) and for LMD, 9 SNPs surpassed the genome-wide significant threshold (P < 1.39E-06). These SNPs explained 30.33 and 27.51% phenotypic variance for BF and LMD respectively. Furthermore, 14 and 9 genes nearest to the significant SNPs were selected to be candidate genes, including MAGED1, GPHN, CCSER1, and GUCY2D for BF and PARM1, COL18A1, HSF5, and SCML2 genes for LMD. One significant SNP, which explained 6.07% of phenotypic variance for BF, mapped to a pleiotropic quantitative trait locus with a 494-kb interval. Together, the SNPs and candidate genes identified in this study will advance our understanding of the complex genetic architecture of BF and LMD traits, and they will also provide important clues for future implementation of a genomic selection program in Chuying-black pigs.

Comparative genome-wide methylation analysis of longissimus dorsi muscles in Yorkshire and Wannanhua pigs.

DNA methylation was one of the earliest discovered epigenetic modifications in vertebrates, and is an important epigenetic mechanism involved in the expression of genes in many biological processes, including muscle growth and development. Its effects on economically important traits are evidenced in reported differences in meat quality traits between Chinese indigenous pig breeds (Wannanhua pig) and Western commercial pig breeds (Yorkshire pig), and this presents a unique model for analyzing the effects of DNA methylation on these traits. In the present study, a whole genome DNA methylation analysis was performed on the two breeds using methylated DNA immunoprecipitation. GO functional enrichment and pathway enrichment analyses identified differentially methylated genes primarily associated with fatty acid metabolism, biological processes of muscle development and signaling pathways related to muscle development and pork quality. Differentially methylated genes were verified by sodium pyrosequencing, and the results were consistent with the sequencing results. The results of the integrative analysis between DNA methylation and gene expression revealed that the DNA methylation levels showed a significantly negative correlation with gene expression levels around the transcription start site of genes. In total, 41 genes were both differentially expressed and methylated; these genes were related to fat metabolism, lipid metabolism and skeletal muscle development. This study could help further explore the molecular mechanisms and phenotypic differences in pig growth and development among different breeds.

MiR-587 acts as an oncogene in non-small-cell lung carcinoma via reducing CYLD expression.

OBJECTIVE: This study aims to explore the cancer-associated functions of microRNA-587 (miR-587) in the development of non-small-cell lung carcinoma (NSCLC) and the molecular mechanism. PATIENTS AND METHODS: Relative expression levels of miR-587 and CYLD in NSCLC samples were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Proliferative and migratory abilities in A549 and H1299 cells with overexpressed miR-587 were examined by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. The regulatory interaction between miR-587 and CYLD was determined by Dual-Luciferase reporter assay and Pearson correlation test. At last, the co-regulation of miR-587 and CYLD on NSCLC cell functions was assessed by rescue experiments. RESULTS: MiR-587 was upregulated in NSCLC samples and closely linked to tumor staging, whereas CYLD was downregulated and negatively correlated to that of miR-587. Survival analysis suggested that miR-587 was an unfavorable factor to the prognosis of NSCLC. Overexpression of miR-587 stimulated proliferative and migratory abilities in A549 and H1299 cells. CYLD was the downstream gene binding miR-587. Overexpression of CYLD could partially abolish the regulatory effects of overexpressed miR-587 on promoting proliferative and migratory abilities in NSCLC cells. CONCLUSIONS: MiR-587 stimulates proliferative and migratory abilities in NSCLC by downregulating CYLD, thus aggravating the progression of NSCLC.

Circular RNA circ_0067934 functions as an oncogene in breast cancer by targeting Mcl-1.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Circular RNA circ_0067934 functions as an oncogene in breast cancer by targeting Mcl-1, by J.-M. Wang, X.-J. Li, J. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (21): 9499-9505-DOI: 10.26355/eurrev_201911_19444-PMID: 31773702" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19444.

METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2.

OBJECTIVE: The aim of this study was to investigate whether METTL3 promoted the progression of nasopharyngeal carcinoma (NPC) by silencing CDKN1C through EZH2. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression level of METTL3 in 48 pairs of NPC tissues and adjacent normal tissues. METTL3 expression in patients with different tumor lymph node metastasis (TNM) stages was detected by qRT-PCR as well. The Kaplan-Meier method was used to analyze the interplay between METTL3 expression and the prognosis of patients with NPC. At the same time, METTL3 expression in normal epithelial cell line (BEAS-2B) and NPC cell lines (SUNE-1 and C666-1) was examined using qRT-PCR. After METTL3 was knocked down in SUNE-1 cells, cell viability and migration abilities were analyzed by cell counting kit-8 (CCK-8) test and wound healing assay, respectively. The mRNA and protein expressions of EZH2 were detected by qRT-PCR and Western blot, respectively. RNA immunoprecipitation (RIP) assay was applied to detect the binding of METTL3 to EZH2 mRNA and the m6A modification on EZH2 mRNA. After knockdown of EZH2 in SUNE-1 cells, qRT-PCR was used to detect the mRNA expression of CDKN1C. Meanwhile, chromatin immunoprecipitation (ChIP) assay was conducted to analyze the binding of EZH2 to the CDKN1C promoter region. After down-regulation of METTL3 in SUNE-1 cells, the protein expressions of EZH2 and CDKN1C were detected using Western blot. After simultaneous knockdown of METTL3 and CDKN1C in SUNE-1 cells, CCK8 assay and wound healing assay were applied to examine cell viability and migration abilities. RESULTS: METTL3 expression in NPC tissues was remarkably higher than that of adjacent normal tissues. Meanwhile, METTL3 expression in T3 and T4 tumors was significantly higher than that of T1 and T2 tumors. In patients with lymph node metastasis, the expression of METTL3 was remarkably higher than those without metastasis. Survival analysis demonstrated that patients with higher expression of METTL3 exhibited significantly longer overall survival time than those with lower METTL3 expression. QRT-PCR revealed that METTL3 was highly expressed in NPC cell lines, including SUNE-1 and C666-1. After knock-down of METTL3 in SUNE-1 cells, cell viability and migration abilities were both markedly weakened. Meanwhile, the protein expression of EZH2 was remarkably reduced. However, no significant changes were observed in EZH2 mRNA level. RIP assay revealed that METTL3 could bind to EZH2 mRNA, and a m6A modification was verified on EZH2 mRNA. After knockdown of EZH2, the mRNA level of CDKN1C in SUNE-1 cells was significantly up-regulated. CHIP assay indicated that EZH2 could bind to CDKN1C. Western blot showed that, after interfering with METTL3 in SUNE-1 cells, the protein expression of EZH2 decreased significantly, while CDKN1C was up-regulated. In addition, simultaneous downregulation of METTL3 and CDKN1C in SUNE-1 cells reversed the influence of METTL3 on cell viability and migration abilities. CONCLUSIONS: METTL3 was highly expressed in NPC tissues, which might inhibit EZH2 expression by mediating M6A modification of EZH2 mRNA. Furthermore, CDKN1C could increase the malignancy of NPC cells and promote the progression of NPC.

LncRNA NEAT1 regulated cell proliferation, invasion, migration and apoptosis by targeting has-miR-376b-3p/SULF1 axis in non-small cell lung cancer.

OBJECTIVE: Recently, lncRNA has been determined to play an important role in cancer formation and development. However, the regulatory mechanism of lncRNA in NSCLC has not been fully explored. PATIENTS AND METHODS: The expression of NEAT1, miR-376b-3p, and SULF1 was detected in each group via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The proteins expression of SULF1, p-MAPK, MAPK, p-Akt, Akt, and GAPDH were measured via Western blot. MTT assay was applied to detect cell proliferation in each group. Transwell assay was used to assess cell invasion and migration of each group. Cell apoptosis was assessed with flow cytometry. The relationship among NEAT1, miR-376b-3p, and SULF1 was determined using Luciferase reporter assay. RESULTS: In this study, the expression of NEAT1 and SULF1 was upregulated in NSCLC tissues and cells. Of note, the knockdown of NEAT1 and SULF1 could inhibit cell proliferation, migration, and invasion and promote cell apoptosis in NSCLC. Moreover, NEAT1 regulated SULF1 expression via binding to miR-376b-3p in NSCLC cells. Otherwise, the effects of NEAT1 on cell growth and apoptosis were reversed by improving the SULF1 expression in NSCLC cells. Meanwhile, si-NEAT1 transfection inhibited MAPK and Akt signaling pathway by modulating SULF1 in NSCLC cells. CONCLUSIONS: In this study, we found that lncRNA NEAT1 regulated cell proliferation, invasion, migration, and apoptosis by targeting has-miR-376b-3p/SULF1 axis in NSCLC. Moreover, the regulatory network of NEAT1 participated in the phosphorylation levels of MAPK and Akt to affect cell progression of NSCLC, providing a new regulatory pathway in the pathogenesis of lung cancer.

Comparison of hepatic epithelioid angiomyolipoma and non-hepatitis B, non-hepatitis C hepatocellular carcinoma on contrast-enhanced ultrasound.

PURPOSE: The purpose of this study was to retrospectively compare the imaging features of hepatic epithelioid angiomyolipoma (HEAML) to those of hepatocellular carcinoma negative for hepatitis B surface antigen and hepatitis C antibody (NBNC-HCC) on contrast-enhanced ultrasound (CEUS) with sulphur hexafluoride microbubbles. MATERIAL AND METHODS: Twenty-two patients (4 men, 18 women) with a mean age of 42.6±10.2 (SD) years (range: 22-63 years) with histopathologically confirmed HEMAL were included in the study. Forty-four patients (30 men, 14 women) with a mean age of 57.3±15.9 years (range: 19-85 years) with histopathologically confirmed NBNC-HCC were randomly selected from our institution's database as a control group. The CEUS characteristics of the two groups were compared. RESULTS: On conventional ultrasound, significant differences in tumor diameter were found between HEAML (4.0±2.0 [SD] cm; range: 1.3-8.9cm) and NBNC-HCC (8.4±4.4 [SD] cm; range: 1.6-18cm) (P<0.001) as well as in degrees of enhancement during the portal (P=0.001) and late phases (P=0.003), contrast distribution (P<0.001) and absence of pseudocaspule (P<0.001). On CEUS, hyperenhancement during the arterial phase was observed in 21/22 (95.5%) HEAMLs and in 43/44 (97.7%) NBNC-HCCs (P>0.999). Homogeneous enhancement was more frequent in HEAMLs (20/22; 90.9%) than in NBNC-HCCs (13/44; 29.6%) (P<0.001). Pseudocapsule was observed in 0/22 HEAMLs (0.0%) and in 36/44 NBNC-HCCs (81.8%) (P=0.017). A prolonged enhancement was observed in 5/22 HEAMLs (22.7%) and in 0/44 NBNC-HCCs (0.0%) (P<0.001) during the late phase. CONCLUSION: CEUS with sulphur hexafluoride microbubbles is helpful in discriminating between HEAML and NBNC-HCC. Homogeneous enhancement and lack of pseudocapsule are suggestive features for the diagnosis of HEAML.

MiR-429-5p attenuates the migration and invasion of malignant melanoma by targeting LIMK1.

OBJECTIVE: To investigate the potential effects of microRNA-429-5p (miR-429-5p) on the development of malignant melanoma (MM) and the relevant mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the differential expression of miR-429-5p in MM tissues. The relationship between miR-429-5p expression and clinical pathological data of MM patients was analyzed. LIM kinase 1 (LIMK1) was verified as a downstream target of miR-429-5p by online prediction software, and the interaction between LIMK1 and miR-429-5p was verified by Dual-Luciferase reporter assay. RESULTS: Compared with normal skin tissues, miR-429-5p was downregulated in MM tissues. MiR-429-5p expression was correlated with tumor size and stage of MM. Upregulation of miR-429-5p significantly inhibited protein expression of LIMK1 and reduced migration and invasion ability of MM cells. LIMK1 was involved in MM progression regulated by miR-429-5p. CONCLUSIONS: MiR-429-5p attenuates migration and invasion in MM by targeting LIMK1. Hence, miR-429-5p/LIMK1 axis might be a potential therapeutic target for the treatment of MM.

Potential association between elevated serum human epididymis protein 4 and chronic kidney disease in female patients.

Serum levels of human epididymis protein 4 (HE4) are elevated in a large number of women with chronic kidney disease (CKD). However, it remains unclear whether HE4 can be used as a potential biomarker for the diagnosis of CKD. This study aims to determine whether serum HE4 is a potential biomarker for CKD in Han Chinese female patients. A total of 347 Han Chinese female patients aged 19 to 89 were included in the present study. Among these patients, 154 were healthy control individuals, while 193 were hospitalized patients with CKD. Their demographic characteristics were obtained, and the levels of serum creatinine (Scr), beta2-microglobulin (B2M), and cystatin C (CysC) (to assess renal function) were measured. Serum HE4 concentration was determined by electrochemiluminescence. Serum HE4 levels in patients with CKD were significantly higher than those in the control group (P < 0.001). Meanwhile, there were significant differences in HE4 levels among the four CKD subgroups (P < 0.001) via multiple comparisons. In addition, the diagnostic value of HE4 was significantly higher than other indicators by ROC curve analysis. HE4 may not only serve as a potential biomarker to predict CKD but also have an important reference value for CKD staging.

Circular RNA circ_0067934 functions as an oncogene in breast cancer by targeting Mcl-1.

OBJECTIVE: Breast cancer (BC) is one of the most ordinary malignant tumors. Recent studies have revealed that long noncoding RNAs (lncRNAs) play an important role in the progression of tumorigenesis. This work aims to identify how circ_0067934 functions in the progression of BC. PATIENTS AND METHODS: Circ_0067934 expression of both 57 paired BC patients' tissue samples and cells was detected by Real Time-quantitative Polymerase Chain reaction (RT-qPCR). Moreover, the function of circ_0067934 was identified by performing proliferation assay, colony formation assay, cell cycle assay, and Ethynyl deoxyuridine (EdU) incorporation assay in vitro. Besides, the underlying mechanism was explored through Western blot assay and RT-qPCR. RESULTS: In this study, circ_0067934 expression was significantly higher in BC tissues when compared with that in adjacent non-tumor samples. Cell proliferation in BC was inhibited after knockdown of circ_0067934 in vitro. Moreover, cell cycle in BC was regulated after knockdown of circ_0067934 in vitro. Results of further experiments revealed that Mcl-1 was downregulated via the knockdown of circ_0067934 in BC. CONCLUSIONS: Our work suggests that circ_0067934 enhances BC cell proliferation and regulates BC cell cycle via upregulating Mcl-1.

MiR-574-3p exerts as a tumor suppressor in ovarian cancer through inhibiting MMP3 expression.

OBJECTIVE: The mortality rate of ovarian cancer (OC) has always been the highest among all female reproductive system malignant tumors. Currently, miRNAs have been verified to participate in the tumorigenesis and prognosis of OC. However, the expression and function of miR-574-3p in OC have not been fully elucidated. PATIENTS AND METHODS: The expression level of miR-574-3p in OC tissues and cells was detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). By transfection of miR-574-3p mimics or inhibitor, the expression of miR-574-3p in SW626 or A2780 cells was up-regulated or down-regulated, respectively. Cell counting kit-8 (CCK-8) and colony formation assays were used to measure the proliferation of transfected OC cells. Meanwhile, the transwell assay was applied to detect the migration and invasion abilities of OC cells. Furthermore, dual-luciferase reporter gene analysis and Western blot were utilized to explore the underlying downstream molecules for miR-574-3p in OC. RESULTS: MiR-574-3p was lowly expressed in OC tissue samples when compared with para-tumor tissues. Meanwhile, the expression of miR-574-3p in OC-derived cells was significantly lower than normal control HOSE cells. The overexpression of miR-574-3p markedly reduced the proliferation, invasion, and migration of SW626 cells. However, the inhibition of miR-574-3p remarkably accelerated the growth and metastasis of A2780 cells. MMP3 was verified as a direct target for miR-574-3p in OC. In addition, miR-574-3p could reduce the protein expression of MMP3 by binding to its 3'-untranslated region (3'-UTR). CONCLUSIONS: MiR-574-3p functioned as a tumor suppressor in OC, which might be served as a potential target for the diagnosis and therapy for OC.

MicroRNA-23b suppresses cervical cancer biological progression by directly targeting six1 and affecting epithelial-to-mesenchymal transition and AKT/mTOR signaling pathway.

OBJECTIVE: To elucidate the effects and mechanism of microRNA-23b (miR-23b) in cervical cancer (CC) progression. PATIENTS AND METHODS: Fifty-six pairs of CC tissue samples and matched para-carcinoma tissue samples were collected. Meanwhile, human normal cervical epithelial cell and CC cell lines were cultured. The abilities of cell proliferation and migration were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays and transwell assays. The correlation between sine oculis homeobox 1 (six1) and miR-23b was clarified by dual-luciferase reporter assay. The relative protein and mRNA expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and Western blot. In addition, Xenograft tumor formation assay was performed in this study. RESULTS: MiR-23b was remarkably down-regulated in CC and the low miR-23b expressions were associated with the poor prognosis and worse OS of CC patients. Additionally, the functional assays demonstrated that miR-23b overexpression obviously repressed CC cell proliferation, invasion and migration abilities through the regulation of the AKT/mTOR pathway and the epithelial-to-mesenchymal transition (EMT) progress. Moreover, the luciferase reporter assay indicated that six1 was one functional target for miR-23b in CC cells, indicating that the inhibitory functions of miR-23b in CC cells were partially regulated by six1. Moreover, miR-23b restoration could prominently repress tumor growth in vivo. CONCLUSIONS: MiR-23b suppressed CC progression via directly targeting six1 and affecting AKT/mTOR signaling pathway as well as EMT progress. Therefore, miR-23b/six1 may be promising biomarkers for CC diagnosis and therapy.