BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

The mechanism of tinnitus remains undear.Currently,in addition to tinnitus induced by ear disea-ses,various systems of the body are also involved in the pathogenesis of tinnitus.Obstructive sleep apnea hypopnea syndrome(OSAHS)may be related to tinnitus,which has garnered increasing attention in recent years.This article reviews the latest research progress on the occurrence and possible mechanism of tinnitus in OSAHS,shedding new light on the treatment of tinnitus.

Objective To explore the characteristics of endometrial lesions and uterine cavity abnormality by transvaginal sonography(TVS)and the potential impact of aging on those. Methods 1052 elderly women(aged ≥60 years)underwent hysteroscopy endometrial curettage based on TVS providing an indication of abnormal uterine cavity at our hospital from January 2010 to December 2017 ,and their clinical and pathological data were analyzed.1052 patients were divided by age into a <65 years group and a ≥65 years group. And age tertile stratifications of lower tertile group ,middle tertile group ,and upper tertile group were used to investigate the correlation between ageing and endometirum diseases. Results A total of 1052 elderly women were included ,and the simple endometrial thickening was the most common etiological factor (53.2％ ) ,followed by abnormal endometrial echoes(36.9％ )and endometrial cavity fluid(9.9％ ).All the pathological results of polyps and endometrial cancer accounted for 57.8％ and 4.2％ ,respectively.Age tertile stratification analysis suggested that the proportions of endometrial cavity fluid was 6.1％ (n=20)in the lower tertile group , 5.9％ (n=20)in the middle tertile group ,and 16.7％ (n=64)in the upper tertile group(χ2 =23.40 ,P<0.01). An increasing proportion along with aging for precancerous lesions was 0.0％ (n=0) ,2.4％(n= 8) ,3.1％ (n = 12)(χ2 = 9.04 ,P < 0.01)in lower/middle/upper age tertile groups.But the proportion of endometrial cancer was decreased with ageing [lower/middle/upper tertiles :6.1％ (n=20) ,4.7％ (n=16) ,2.1％ (n=8)(χ2 =7.23 ,P<0.01]. Conclusions TVS is an effective methodfor screening uterine cavity lesions in elderly women. The TVS-detected prevalence of endometrial cavity fluid increases with ageing. The hysteroscopy endometrial pathological examination shows that endometrial cancer decreases and precancerous lesions increase with ageing.

An aromatase encoded by the CYP19 gene catalyzes the final step in the biosynthesis of estrogens, which is related to endometriosis development. To assess the association of CYP19 gene polymorphisms with the risks of endometriosis, chocolate cysts and endometriosis-related infertility, a case-control study was conducted in Chinese Han women by recruiting 225 healthy control females, 146 patients with endometriosis, 94 endometriosis women with chocolate cyst and 65 women with infertility resulting from endometriosis, as diagnosed by both pathological and laparoscopic findings. Individual genotypes at rs2236722:T>C, rs700518:A>G, rs10046:T>C and [TTTA]n polymorphisms were identified. Allelic and genotypic frequencies were compared between the control group and case groups by chi-square analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined by logistic regression analysis to predict the association of CYP19 gene polymorphisms with the risk of endometriosis, the related chocolate cysts and infertility. The genotype distributions of the tested CYP19 gene polymorphisms were not significantly different between the healthy control group and the endometriosis/endometriosis with the chocolate cyst group. However, the CYP19 rs700518AA genotype was significantly associated with an increased risk of endometriosis-related infertility (55.4% in the infertility group vs 25.3% in the control group, P<0.001; OR (95% CI): 3.66 (2.06-6.50)) under the recessive form of the A allele. Therefore, we concluded that in Chinese Han females CYP19 gene polymorphisms are not associated with susceptibility to endometriosis or chocolate cysts, whereas CYP19 rs700518AA genotype confers genetic susceptibility to endometriosis-related infertility.
Adult ; Aromatase/*genetics ; Case-Control Studies ; China ; Endometriosis/complications/*genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Infertility, Female/complications/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide

Objective To observe the relationship between vasoactive substances and blood pressure in old patients with hypertension.Method Venous blood was drawn from 35 old hypertension patients when blood pressure was normal and abnormal,respectively.Epinephrine(E),norepinephine(NE),endothelins(ET),angiotensin ll (Angll) and ealcitonin-gene-retated peptide were determined by radio-immunity.The above five cytokines were also determined in 33 old healthy people.The cytokines levels were compared between the normal and abnormal blood pressure in hypertension patients and also between the old hypertension patients and healthy persons.The correlation between blood pressure and cytokines were analyzed.Results The level of ET,Angll,E and NE were obviously increased in old hypertension patients when their blood pressure was abnormal,while CGRP obviously decreased.No difference was found in the five cytokines between two groups when the blood pressure were normal.The correlation analysis showed that systolic pressure had positive correlation with ET,AnglI and E(r=0.304,0.337,0.587,P=0.031,0.019,0.036)and negative correlation with CGRP(r=-0.416,P=0.028)in old hypertension patients when the blood pressure was abnormal.And the diastolic pressure had positive correlation with AnglI and E(r=0.357,0.333;P=0.039,0.028).ET had positive correlation with Angll and E(r=0.361,0.315;P=0.041,0.029).Conclusion The levels of vasoaetive substances significantly changed in old hypertension patients with the blood pressure change.Among those cytokines,the substances that contract blood vessel increased most obviously.The vasoactive substances played an important role in the progress of blood pressure rising.