LncRNA OIP5-AS1 Upregulates the Cyclin D2 Levels to Promote Metastasis of Breast Cancer by Targeting miR-150-5p.

OBJECTIVE: Breast cancer (BC) is a cancer that seriously affects women's health. BC cell migration increases the mortality of BC patients. Current studies have shown that long noncoding RNAs (LncRNAs) are related to the metastasis mechanism of BC. This study aimed to explore the function and role of LncRNA OIP5-AS1 in BC. And we analyzed its regulatory mechanism and related modification process. METHODS: Our study analyzed the expression pattern of OIP5-AS1 in BC tissues and cell lines by qRT-PCR. The effects of OIP5-AS1 on the function of BC cells were detected by CCK-8 and transwell experiments. Bioinformatics analysis and double luciferase reporter gene detection were used to confirm the correlation between OIP5-AS1 and miR-150-5p and between miR-150-5p and Cyclin D2 (CCND2). The rescue test analyzed the effect of miR-150-5p regulating OIP5-AS1. In addition, the N6-methyladenosine (m6A) modification process of OIP5-AS1 was analyzed by RNA m6A dot blot, RIP assay, and double luciferase report experiment. RESULTS: OIP5-AS1 was significantly upregulated in BC tissues and cell lines. OIP5-AS1 knockdown inhibited BC cell viability, migration and invasion. OIP5-AS1 upregulated CCND2 by binding with miR-150-5p. This process affected the metastasis of BC. Higher degree of m6A methylation was confirmed in BC cell lines. There were some binding sites between methyltransferase like 3 (METTL3) and OIP5-AS1. Moreover, the silencing of METTL3 inhibited the OIP5-AS1 expression through decreasing the m6A methylation levels. CONCLUSIONS: LncRNA OIP5-AS1 promoted cell viability and metastasis of BC cells by targeting miR-150-5p/CCND2 axis. This process was modified by m6A methylation of METTL3.

Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism. / è‚¾ä¸Šè ºå—œé“¬ç»†èƒžç˜¤å½±å“ä¸‰æ¡ä¸»è¦ä»£è°¢é€šè·¯ï¼šåŠèƒ±æ°¨é ¸-è›‹æ°¨é ¸ä»£è°¢ã€å˜§å•¶ä»£è°¢å’Œé ªæ°¨é ¸ä»£è°¢é€šè·¯.

Pheochromocytomas and paragangliomas (PPGLs) cause symptoms by altering the circulation levels of catecholamines and peptide hormones. Currently, the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines. In this study, we used ultra-performance liquid chromatography (UPLC)/quadrupole time-of-flight mass spectrometry (Q-TOF MS) analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients. We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla. Through conducting two steps of metabolomics analysis, we identified 111 differential metabolites between the healthy group and the patient group, among which 53 metabolites were validated. By integrating the information of differential metabolites and differentially expressed genes, we inferred that the cysteine-methionine, pyrimidine, and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm. The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma, whereas the pyrimidine pathway showed no significant difference. Finally, we developed an optimized diagnostic model of two metabolites, L-dihydroorotic acid and vanylglycol. Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.

A case of primary aldosteronism with rhabdomyolysis in which the first symptoms were thyrotoxicosis and peripheral paralysis and literature review.

Background: Primary aldosteronism (PA) is one of the main causes of secondary endocrine hypertension, especially refractory hypertension. Increased autonomous secretion leads to increased blood pressure and proinflammatory effects on different organ systems, including the cardiovascular system. However, because of its diverse clinical manifestations or the combination of other conditions, it sometimes causes problems for correct diagnosis. Therefore, we report and review the characteristics of some atypical and uncommon special case cases related to proaldosterone to provide clinical ideas for correct diagnosis and decision-making of proaldosterone. Case Description: A 38-year-old male patient with fatigue and bilateral lower extremity pain came to the clinic and was found to have abnormal thyroid function, low blood potassium, elevated blood pressure, and also combined with rhabdomyolysis (RM) after further improvement of functional tests and imaging tests was diagnosed with an adrenal cortical adenoma (aldosteronism), hypertension secondary to PA, hypokalemia secondary to PA, RM, and subacute thyroiditis. After laparoscopic resection of a unilateral adrenal adenoma, the patient's blood pressure and blood potassium gradually returned to normal, and thyroid function returned to normal without additional intervention. Conclusions: Early screening should be performed for the high-risk population of PA to prevent the occurrence of RM and other serious complications caused by the progression of the disease. For patients with RM, the primary disease should be approached radically and should be based on symptomatic treatment. For RM syndrome associated with thyroid dysfunction, the etiology of the thyroid dysfunction should be actively identified to guide appropriate clinical management.

Visualization and metabolome for the migration and distribution behavior of pesticides residue in after-ripening of banana.

Exploring the behavior of pesticide residues in fruits is important for effectively applying pesticides and minimizing the risk of pesticide exposure to humans. However, most studies do not consider in situ visual analysis of residues and migration patterns in fresh fruit samples. We investigated the migration patterns of thiram, propamocarb, imidacloprid and pyraclostrobin in fresh bananas based on ambient mass spectrometry imaging, metabolome and transcriptome analysis. The systemic pesticides entered via lateral penetration and vertical migration over time, which began to internally migrate to the inner core after 6 h. The non-systemic pesticide thiram did not enter the interior of the bananas, and remained only in the peel. The transportation rate of the pesticides increased with the decrease of water-octanol partition coefficient and the relative molecular mass. Moreover, the pesticide migrated fast with the increase of banana ripeness. The pesticides significantly enhanced pyruvate kinase, NADP-dependent malic enzyme, and malate synthase activities in the banana peels through carbohydrate metabolism. The banana pulp was also protected against the external toxicity of pesticides by the ascorbate-glutathione cycle. These results can provide guidelines for the appropriate application of pesticides and their safety evaluation.

Early prediction of pathological complete response to neoadjuvant chemotherapy combining DCE-MRI and apparent diffusion coefficient values in breast Cancer.

INTRODUCTION: Improving the early prediction of neoadjuvant chemotherapy (NAC) efficacy in breast cancer can lead to an improved prediction of the final prognosis of patients, which would be useful for promoting individualized treatment. This study aimed to explore the value of the combination of dynamic contrast-enhanced (DCE)-MRI parameters and apparent diffusion coefficient (ADC) values in the early prediction of pathological complete response (pCR) to NAC for breast cancer. METHODS: A total of 119 (range, 28-69 years) patients with biopsy-proven breast cancer who received two cycles of NAC before breast surgery were retrospectively enrolled from our hospital database. Patients were divided into pCR and non pCR groups according to their pathological responses; a total of 24 patients achieved pCR, while 95 did not. The quantitative (Ktrans; Kep; Ve; IAUC) and semiquantitative parameters (W-in; W-out; TTP) of DCE-MRI that were significantly different between groups were combined with ADC values to explore their value in the early prediction of pCR to NAC for breast cancer. The independent T test was performed to compare the differences in DCE-MRI parameters and ADC values between the two groups. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC), sensitivity and specificity were calculated to evaluate the performance of the prediction. RESULTS: The Ktrans, Kep, IAUC, ADC, W-in and TTP values were significantly different between the pCR and non pCR groups after NAC. The AUC (0.845) and specificity (95.79%) of the combined Ktrans, Kep, IAUC and ADC values were both higher than those of the individual parameters. The combination of W-in, TTP and ADC values had the highest AUC value (0.886) in predicting pCR, with a sensitivity and specificity of 87.5% and 82.11%, respectively. CONCLUSIONS: The results suggested that the combination of ADC values and quantitative and semiquantitative DCE-MRI parameters, especially the combination of W-in, TTP, and ADC values, may improve the early prediction of pCR in breast cancer.

Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients.

OBJECTIVE: To investigate the prevalence and spectrum of BRCA1 and BRCA2 mutations in Chinese Hakka patients with breast and ovarian cancer. METHODS: A total of 1,664 breast or ovarian cancer patients were enrolled for genetic testing at our hospital. Germline mutations of the BRCA gene were analysed by next-generation sequencing, including the coding regions and exon intron boundary regions. RESULTS: The 1,664 patients included 1,415 (85.04%) breast cancer patients and 245 (14.72%) ovarian cancer patients, while four (0.24%) patients had both the breast and ovarian cancers. A total of 151 variants, including 71 BRCA1 variants and 80 BRCA2 variants, were detected in the 234 (14.06%) patients. The 151 variants included 58 pathogenic variants, 8 likely pathogenic variants, and 85 variants of unknown significance (VUS). A total of 56.25% (18/32) and 65.38% (17/26) of pathogenic variants (likely pathogenic variants are not included) were distributed in exon 14 of BRCA1 and exon 11 of BRCA2, respectively. The most common pathogenic variants among this Hakka population are c.2635G > T (p.Glu879*) (n = 7) in the BRCA1 gene and c.5164_5165del (p.Ser1722Tyrfs*4) (n = 7) in the BRCA2 gene among the Hakka population. A hotspot mutation in the Chinese population, the BRCA1 c.5470_5477del variant was not found in this Hakka population. The prevalence and spectrum of variants in the BRCA genes in the Hakka patients are different from that in other ethnic groups. CONCLUSIONS: The most common pathogenic variant in this population is c.2635G > T in the BRCA1 gene, and c.5164_5165delAG in the BRCA2 gene in this population. The prevalence and spectrum of variants in the BRCA1 and BRCA2 genes in the Hakka patients from southern China are different from those in other ethnic groups.

Identification and validation of a novel zinc finger protein-related gene-based prognostic model for breast cancer.

BACKGROUND: Breast invasive carcinoma (BRCA) is a commonly occurring malignant tumor. Zinc finger proteins (ZNFs) constitute the largest transcription factor family in the human genome and play a mechanistic role in many cancers' development. The prognostic value of ZNFs has yet to be approached systematically for BRCA. METHODS: We analyzed the data of a training set from The Cancer Genome Atlas (TCGA) database and two validation cohort from GSE20685 and METABRIC datasets, composed of 3,231 BRCA patients. After screening the differentially expressed ZNFs, univariate Cox regression, LASSO, and multiple Cox regression analysis were performed to construct a risk-based predictive model. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and gene set enrichment analyses (GSEA) were utilized to assess the potential relations among the tumor immune microenvironment and ZNFs in BRCA. RESULTS: In this study, we profiled ZNF expression in TCGA based BRCA cohort and developed a novel prognostic model based on 14 genes with ZNF relations. This model was composed of high and low-score groups for BRCA classification. Based upon Kaplan-Meier survival curves, risk-status-based prognosis illustrated significant differences. We integrated the 14 ZNF-gene signature with patient clinicopathological data for nomogram construction with accurate 1-, 3-, and 5-overall survival predictive capabilities. We then accessed the Genomics of Drug Sensitivity in Cancer database for therapeutic drug response prediction of signature-defined BRCA patient groupings for our selected TCGA population. The signature also predicts sensitivity to chemotherapeutic and molecular-targeted agents in high- and low-risk patients afflicted with BRCA. Functional analysis suggested JAK STAT, VEGF, MAPK, NOTCH TOLL-like receptor, NOD-like receptor signaling pathways, apoptosis, and cancer-based pathways could be key for ZNF-related BRCA development. Interestingly, based on the results of ESTIMATE, ssGSEA, and GSEA analysis, we elucidated that our ZNF-gene signature had pivotal regulatory effects on the tumor immune microenvironment for BRCA. CONCLUSION: Our findings shed light on the potential contribution of ZNFs to the pathogenesis of BRCA and may inform clinical practice to guide individualized treatment.

Changing Patterns in Clinicopathological Characteristics of Breast Cancer and Prevalence of BRCA Mutations: Analysis in a Rural Area of Southern China.

PURPOSE: Although the burden of breast cancer remains especially high in rural China, data on the clinicopathological characteristics and prevalence of the breast cancer susceptibility gene 1/2 (BRCA1/2) mutations in patients with breast cancer remain limited. We investigated the clinicopathological characteristics, changing patterns, and prevalence of BRCA1/2 mutations in patients with breast cancer. PATIENTS AND METHODS: The clinicopathological characteristics of 3712 women with pathologically confirmed primary breast cancer treated at Meizhou People's Hospital between January 2005 and December 2018 were evaluated. The prevalence of BRCA1/2 mutations in 340 patients with breast cancer diagnosed between January 2017 and September 2018 was also evaluated. RESULTS: The median age at diagnosis was 49±10.5 (range, 20-94) years. Positivity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was observed in 59.0%, 52.5%, and 24.9% of patients, respectively. Time trend analysis revealed that an increasing trend was observed for age at diagnosis (p = 0.001), proportion of patients without a reproductive history (p < 0.001), postmenopausal patients (p = 0.001), invasive pathological cancer type (p = 0.008), ER-positive rate (p < 0.001), PR-positive rate (p = 0.008), and HER2-positive rate (p < 0.001). Compared with patients without BRCA1/2 mutations, those with BRCA1/2 mutations were more likely to have a family history of breast or ovarian cancer (p < 0.001) and have triple-negative breast cancer (TNBC) (p < 0.001). Family history of breast or ovarian cancer (odds ratio [OR], 103.58; 95% confidence interval [CI], 20.58-521.45; p < 0.001) and TNBC subtype (OR, 5.97; 95% CI, 1.16-30.90; p = 0.033) were independent predictors for BRCA1/2 mutation. CONCLUSION: The clinicopathological characteristics of patients with breast cancer in this rural area have changed during the past decade. BRCA1/2 testing should be performed in patients with breast cancer with a family history of breast or ovarian cancer and TNBC.