Crosstalk among Alternative Polyadenylation, Genetic Variants and Ubiquitin Modification Contribute to Lung Adenocarcinoma Risk.

Ubiquitin modification and alternative polyadenylation play crucial roles in the onset and progression of cancer. Hence, this study aims to comprehensively and deeply understand gene regulation and associated biological processes in lung adenocarcinoma (LUAD) by integrating both mechanisms. Alternative polyadenylation (APA)-related E3 ubiquitin ligases in LUAD were identified through multiple databases, and the association between selected genetic loci influencing gene expression (apaQTL-SNPs) and LUAD risk were evaluated through the GWAS database of the Female Lung Cancer Consortium in Asia (FLCCA). Subsequently, the interaction between RNF213 and ZBTB20, as well as their functional mechanisms in LUAD, were investigated using bioinformatics analysis, Western blot, co-immunoprecipitation, and colony formation experiments. A total of five apaQTL-SNPs (rs41301932, rs4494603, rs9890400, rs56066320, and rs41301932), located on RNF213, were significantly associated with LUAD risk (p < 0.05), and they inhibit tumor growth through ubiquitin-mediated degradation of ZBTB20.

Perinatal maternal factors influencing postpartum feeding practices at six weeks.

OBJECTIVE: Despite the World Health Organization's recommendation of exclusive breastfeeding for the initial 6 months, breastfeeding rates decline within the first 6 weeks after delivery. This study aimed to (1) investigate the breastfeeding rate at 6 weeks postpartum and (2) explore the influence of perinatal factors on feeding patterns at 6 weeks postpartum. METHOD: A total of 635 participants were enrolled from February to August 2023 at outpatient clinics in three tertiary hospitals in Nantong City. Variables were collected through questionnaires during the third trimester of pregnancy, including demographic information, pregnancy stress, anxiety, depression, sleep, and resilience. At 6 weeks postpartum, information regarding feeding patterns, delivery and postpartum situations, postpartum stress, anxiety, depression, sleep, and resilience was gathered. Initial single-factor analyses were conducted using feeding pattern as the dependent variable, and variables with significance were chosen as independent variables. The disordered multi-classification logistic regression model was then established using the stepwise forward method. RESULTS: Within the first 6 weeks, 35.28% (224/635) of postpartum women exclusively breastfed their infants. Factors influencing exclusive breastfeeding and formula feeding at 6 weeks postpartum included breast pain, sleep quality, mental resilience, difference between postpartum and late pregnancy anxiety, insufficient milk supply, and maternal herself caring for the infant (P < 0.05). Factors influencing the transition from exclusive to partial breastfeeding were insufficient milk supply and maternal herself caring for the infant (P < 0.05). CONCLUSION: The study reveals a relative low rate of exclusive breastfeeding in China's first 6 weeks postpartum, along with a comparison of perinatal factors affecting three different feeding patterns. Our findings may contribute additional evidence to the association between perinatal factors and feeding patterns. This study guides healthcare professionals in developing strategies to promote exclusive breastfeeding and improve personalized counseling for exclusive breastfeeding and mental health.

Plasma GPI and PGD are associated with vascular normalization and may serve as novel prognostic biomarkers for lung adenocarcinoma: Multi-omics and multi-dimensional analysis.

The aim of this study was to explore potential novel plasma protein biomarkers for lung adenocarcinoma (LUAD). A plasma proteomics analysis was carried out and candidate protein biomarkers were validated in 102 LUAD cases and 102 matched healthy controls. The same LUAD tumor tissues were detected to explore the correlation between the expression of candidate proteins in tissues and plasma and vascular normalization. A LUAD active metastasis mice model was constructed to explore the role of candidate proteins for lung metastasis. GPI and PGD were verified to be upregulated in plasma from LUAD patients, and the expression of GPI in tumor tissue was positively correlated with the expression of GPI in plasma and negatively correlated with the normalization of tumor blood vessels. Meanwhile, a negative correlation between the expression of GPI and PGD in plasma and tumor vascular normalization was discovered. In the LUAD active metastasis model, the lowest levels of vascular normalization and the highest expression of GPI and PGD were found in mice with lung metastases. This study found that GPI and PGD may be potential plasma biomarkers for LUAD, and monitoring those may infer the risk of metastasis and malignancy of the tumor. SIGNIFICANT: We identified GPI and PGD as potential novel diagnostic and prognostic biomarkers for LUAD. PGD and GPI can be used as diagnostic biomarkers in combination with other available strategies to assist in the screening and diagnosis of LUAD, and as prognostic biomarkers aid in predict the risk of tumor metastasis and malignancy in patients with LUAD.

Integrating apaQTL and eQTL analysis identifies a potential causal variant associated with lung adenocarcinoma risk in the Chinese population.

Alternative polyadenylation (APA) plays a crucial role in cancer biology. Here, we used data from the 3'aQTL-atlas, GTEx, and the China Nanjing Lung Cancer GWAS database to explore the association between apaQTL/eQTL-SNPs and the risk of lung adenocarcinoma (LUAD). The variant T allele of rs277646 in NIT2 is associated with an increased risk of LUAD (OR = 1.12, P = 0.015), lower PDUI values, and higher NIT2 expression. The 3'RACE experiment showed multiple poly (A) sites in NIT2, with the rs277646-T allele causing preferential use of the proximal poly (A) site, resulting in a shorter 3'UTR transcript. This leads to the loss of the hsa-miR-650 binding site, thereby affecting LUAD malignant phenotypes by regulating the expression level of NIT2. Our findings may provide new insights into understanding and exploring APA events in LUAD carcinogenesis.

NEDD4L mediates ITGB4 ubiquitination and degradation to suppress esophageal carcinoma progression.

The ubiquitination-mediated protein degradation exerts a vital role in the progression of multiple tumors. NEDD4L, which belongs to the E3 ubiquitin ligase NEDD4 family, is related to tumor genesis, metastasis and drug resistance. However, the anti-tumor role of NEDD4L in esophageal carcinoma, and the potential specific recognition substrate remain unclear. Based on public esophageal carcinoma database and clinical sample data, it was discovered in this study that the expression of NEDD4L in esophageal carcinoma was apparently lower than that in atypical hyperplastic esophageal tissue and esophageal squamous epithelium. Besides, patients with high expression of NEDD4L in esophageal carcinoma tissue had longer progression-free survival than those with low expression. Experiments in vivo and in vitro also verified that NEDD4L suppressed the growth and metastasis of esophageal carcinoma. Based on co-immunoprecipitation and proteome analysis, the NEDD4L ubiquitination-degraded protein ITGB4 was obtained. In terms of the mechanism, the HECT domain of NEDD4L specifically bound to the Galx-ß domain of ITGB4, which modified the K915 site of ITGB4 in an ubiquitination manner, and promoted the ubiquitination degradation of ITGB4, thus suppressing the malignant phenotype of esophageal carcinoma.

Multi-omics and multi-stages integration identified a novel variant associated with silicosis risk.

Assessing the association between candidate single-nucleotide polymorphisms (SNPs) identified by multi-omics approaches and susceptibility to silicosis. RNA-seq analysis was performed to screen the differentially expressed mRNAs in the fibrotic lung tissues of mice exposed to silica particles. Following this, we integrated the SNPs located in the above human homologenes with the silicosis-related genome-wide association study (GWAS) data to select the candidate SNPs. Then, expression quantitative trait locus (eQTL)-SNPs were identified by the GTEx database. Next, we validated the associations between the functional eQTL-SNPs and silicosis susceptibility by additional case-control study. And the contribution of the identified SNP and its host gene in the fibrosis process was further validated by functional experiments. A total of 12 eQTL-SNPs were identified in the screening stage. The results of the validation stage suggested that the variant T allele of rs419540 located in IL12RB1 significantly increased the risk of developing silicosis [additive model: odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.11-2.85, P = 0.017]. Furthermore, the combination of GWAS and the results of validation stage also indicated that the variant T allele of rs419540 in IL12RB1 was associated with increased silicosis risk (additive model: OR = 2.07, 95% CI 1.38-3.12, P < 0.001). Additionally, after knockdown or overexpression of IL12RB1, the levels of pro-inflammatory factors, such as IL-12, IFN-γ, and other pro-inflammatory factors, were correspondingly decreased or increased. The novel eQTL-SNP, rs419540, might increase the risk of silicosis by modulating the expression levels of IL12RB1.

Integration of apaQTL and eQTL analysis reveals novel SNPs associated with occupational pulmonary fibrosis risk.

To explore the association between apaQTL/eQTL-SNPs and the susceptibility to silicosis. A silicosis-related GWAS was initially conducted to screen for single nucleotide polymorphisms (SNPs) associated with the risk of silicosis. Candidate SNPs with apaQTL and eQTL functions were then obtained from the 3'aQTL-atlas and GTEx databases. Subsequently, additional case-control studies were performed to validate the relationship between the candidate apaQTL/eQTL-SNPs and the risk of silicosis. Finally, experiments were conducted to illustrate APA events occurring at different alleles of the identified apaQTL/eQTL-SNPs. The combined results of the GWAS and iMLDR validations indicate that the variant T allele of the rs2974341 located on SMIM19 (additive model: OR = 0.66, the 95% CI = 0.53-0.84, P = 0.001) and the variant T allele of the rs2390488 located on TMTC4 (additive model: OR = 0.72, 95% CI = 0.57-0.90, P = 0.005) were significantly associated with decreased risk of developing silicosis susceptibility. Furthermore, 3'RACE experiments verified the presence of two poly (A) sites (proximal and distal) in SMIM19, rs2974341 may remotely regulate the binding between miRNA-3646 and SMIM19 with its high LD locus rs2974353 to affect the expression level of SMIM19. The rs2974341 variant T allele may contribute to the generation of the shorter 3'UTR transcript of SMIM19 and affect the binding of miRNA-3646 to the target gene SMIM19. The apaQTL/eQTL-SNPs may provide new perspectives for evaluating the regulatory function of SNPs in the development of silicosis.

Identification of the consistently differential expressed hub mRNAs and proteins in lung adenocarcinoma and construction of the prognostic signature: a multidimensional analysis.

BACKGROUND: This study aimed to elucidate the consistency of differentially expressed hub mRNAs and proteins in lung adenocarcinoma (LUAD) across populations and to construct a comprehensive LUAD prognostic signature. METHODS: The transcriptomic and proteomics data from different populations were standardized and analyzed using the same criteria to identify the consistently differential expressed mRNAs and proteins across genders and races. We then integrated prognosis-related mRNAs with clinical, pathological, and EGFR (epidermal growth factor receptor) mutation data to construct a survival model, subsequently validating it across populations. Through plasma proteomics, plasma proteins that consistently differential expressed with LUAD tissues were screened and validated, with their associations discerned by measuring expressions in tumor tissues and tumor vascular normalization. RESULTS: The consistency rate of differentially expressed mRNAs and proteins was ~20-40%, with ethnic factors leading to about 40-60% consistency of differentially expressed mRNA or protein across populations. The survival model based on the identified eight hub mRNAs as well as stage, smoking status, and EGFR mutations, demonstrated good prognostic prediction capabilities in both Western and East Asian populations, with a higher number of unfavorable variables indicating poorer LUAD prognosis. Notably, GPI expression in tumor tissues was inversely correlated with vascular normalization and positively correlated with plasma GPI expression. CONCLUSION: Our study underscores the significance of integrating transcriptomics and proteomics data, emphasizing the need to account for genetic diversity among ethnic groups. The developed survival model may offer a holistic perspective on LUAD progression, enhancing prognosis and therapeutic strategies.

The potential health effects associated with electronic-cigarette.

A good old gateway theory that electronic-cigarettes (e-cigarettes) are widely recognized as safer tobacco substitutes. In actuality, demographics also show that vaping cannibalizes smoking, the best explanation of the data is the "common liability". However, the utilization of e-cigarette products remains a controversial topic at present. Currently, there has been a widespread and substantial growth in e-cigarette use worldwide owing to their endless new flavors and customizable characteristics. Furthermore, e-cigarette has grown widespread among smokers as well as non-smokers, including adolescents and young adults. And some studies have shown that e-cigarette users are at greater risk to start using combustible cigarettes while e-cigarettes use was also observed the potential benefits to people who want to quit smoking or not. Although it is true that e-cigarettes generally contain fewer toxic substances than combustible cigarettes, this does not mean that the chemical composition in e-cigarettes aerosols poses absolutely no risks. While concerns about toxic substances in e-cigarettes and their widespread use in the population are reasonable, it is also crucial to consider that e-cigarettes have been associated with the potential for promoting smoking cessation and the clinically relevant improvements in users with smoking-related pathologies. Meanwhile, there is still short of understanding of the health impacts associated with e-cigarette use. Therefore, in this review, we discussed the health impacts of e-cigarette exposure on oral, nasal, pulmonary, cardiovascular systems and brain. We aspire for this review to change people's previous perceptions of e-cigarettes and provide them with a more balanced perspective. Additionally, we suggest appropriate adjustments on regulation and policy for e-cigarette to gain greater public health benefits.

Cost-effectiveness analysis of antiretroviral drugs for treatment-naive HIV infection in China.

INTRODUCTION: Dolutegravir (DTG)-based regimen was included in the expanded formulary of China's National Free Antiretroviral Treatment Program at the end of 2021. Yet high price of DTG and lack of health economic evaluation in China present barriers for implementation of the regimen. The study aims to investigate the lifetime cost-effectiveness of DTG-based regimen for treatment-naive HIV infection in China. METHODS: A decision-analytic Markov model was used to obtain the costs and effectiveness of four regimens: Arm A, efavirenz (EFV)-based regimen; Arm B, DTG-based regimen; Arm C, elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/c/FTC/TAF) regimen; Arm D, abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) regimen. The potential impact of national centralized drug procurement policy was assessed in scenario analysis. The results were further validated through sensitivity analysis. RESULTS: Compared with other three regimens, DTG-based regimen led to the fewest cumulative adverse reactions, opportunistic infections and deaths. Compared with EFV-based regimen, the base-case ICERs for DTG-based regimen were 13,357 (USD/QALY) and 13,424 (USD/QALY) from the healthcare system and societal perspective respectively. In the policy scenario analysis with the procurement price of DTG equal to that of LPV/r, DTG-based regimen would be dominant. The model results remained robust in sensitivity analyses. CONCLUSIONS: DTG-based regimen for treatment-naive patients is likely to be cost-effective and deserve wider implementation in China. This study strongly suggests the centralized procurement of DTG to minimize cost and maximize cost-effectiveness.

A novel APA-based prognostic signature may predict the prognosis of lung adenocarcinoma in an East Asian population.

The role of alternative polyadenylation (APA) in tumor development is becoming increasingly evident, but the impact of APA events on the prognosis of LUAD patients is unclear. Therefore, in the present study, we aimed to analyze specific APA events in LUAD to identify novel prognostic biomarkers for LUAD. We first identified prognostic candidate genes for LUAD associated with APA events and validated them in both the East Asian and the USA cohorts, finding that five genes (DCUN1D5, PSMC4, TFAM, THRA, and TMEM100) were of prognostic significance in both populations. Based on this, an APA-based prognostic signature was constructed for the East Asian population. The predictive accuracy of the prognostic signature was further evaluated by the time-dependent ROC, with 1-, 2-, and 3-year AUCs of 0.86, 0.81, and 0.71, respectively. This study may provide new markers for individualized diagnosis and prognostic assessment of LUAD and potential targets for precision treatment.

An Observational Study on HIV and Syphilis Rates and Associated Risk Factors among Elderly Men in Wuxi, China.

BACKGROUND: Acquired Immune Deficiency Syndrome (AIDS) remains a nationwide health problem in China; there were a reported 1,045,000 people living with Human immunodeficiency virus (HIV)/AIDS by the end of October 2020, and the proportion of individuals aged 50 years and older living with HIV has also increased from 8% to 24% over the past two decades. METHODS: A cross-sectional study and an 1:2 matched case-control study were conducted from July to August 2016, in Wuxi city, eastern China. A total of 1,000 men aged 50 years and older completed a face-to-face interview regarding their AIDS-related knowledge and attitudes, as well as risk behaviors. RESULTS: Prevalence was 0.1% for HIV and 2% for syphilis. The awareness rate of AIDS-related knowledge among elderly men was 48.9% (range 40.7%-63.9%). The 1꞉2 matched case-control study indicated that only the AIDS-related attitudes were different between the two groups (χ2=8.726, P=0.013), the conditional logistic regression analysis indicated that scores of AIDS health knowledge were the only significant prognostic factor for the infection (HR=0.754 (0.569- 0.999), P=0.049). CONCLUSION: It was crucial to prevent HIV/AIDS and syphilis infections by improving the awareness of AIDS-related knowledge and changing related attitudes among the elderly. Further research aimed at identifying how these factors impact their sexual decision-making can shed valuable insight into further prevention program in this population.

The Impact of Customized Short Message Service on High-Risk Behaviors Among MSM in China, a Randomized Controlled Trial Study.

An individual based randomized controlled trial (RCT) was designed to evaluate the impact of a customized short message service (SMS) intervention on HIV-related high-risk behaviors among Men who have sex with men (MSM). In total, 631 HIV-negative MSM were enrolled at baseline and divided into intervention and control groups randomly. Nine months later, the intervention group who received additional customized SMS intervention reported significantly lower rates of multiple partners, unclear partner infection status and condomless anal intercourse compared to the control group who received the routine intervention only. Six months post stopping the SMS intervention, the rates of unclear partner infection status and condomless anal intercourse still remained lower report in the intervention group. Our study shown that the customized SMS interventions can significantly reduce the HIV-related high-risk behaviors among MSM and with sustained effects over a period of time.

A Novel apaQTL-SNP for the Modification of Non-Small-Cell Lung Cancer Susceptibility across Histological Subtypes.

Background: Alternative polyadenylation (APA) events may be modulated by single nucleotide polymorphisms (SNPs). Therefore, this study aims to evaluate the association between APA quantitative trait loci (apaQTLs)-related SNPs (apaQTL-SNPs) and non-small-cell lung cancer (NSCLC) risk. Methods: APA-related genes associated with NSCLC (LUAD and LUSC) were first identified, and the respective apaQTL-SNPs of those genes were selected. Then, a two-phase case-control study was performed to evaluate the association between candidate apaQTL-SNPs and NSCLC risk. Results: A total of 7 LUAD- and 21 LUSC-associated apaQTL-SNPs were selected. In the first phase, the apaQTL-SNP rs10138506 was significantly associated with LUAD risk (p < 0.05), whereas the other two apaQTL-SNPs (rs1130698 and rs1130719) were significantly associated with LUSC risk (p < 0.05). In the second phase, the variant G allele of rs10138506 was still significantly associated with an increased risk of LUAD (OR = 1.42, 95%CI = 1.02−1.98, p = 0.038). Functional annotation indicated that the variant G allele of rs10138506 was significantly associated with a higher PDUI value of CHURC1. Meanwhile, 3'RACE experiments verified the presence of two poly(A) sites (proximal and distal) in CHURC1, while qRT-PCR results indicated that different genotypes of rs1127968 which, in perfect LD with rs10138506, can mediate changes in the lengths of the 3'UTR of CHURC1 isoforms. Conclusion: The variant G allele of rs10138506 in CHURC1 was correlated with a longer 3'UTR of CHURC1 mRNA and an increased LUAD risk. Further studies should evaluate the interaction between rs10138506 and different 3'UTR lengths of CHURC1 that regulate LUAD development.

Identification of novel lncRNAs associated with sensitivity of HIV antiretroviral therapy: A two-stage matched case-control study.

BACKGROUND: To identify long non-coding RNAs (lncRNAs) that may be used as potential biomarkers of sensitivity to antiretroviral therapy (ART) against human immunodeficiency virus (HIV) infection. METHOD: A two-stage matched case-control study was conducted. First, in the screening stage, peripheral blood lymphocytes (PBLs) of six subjects receiving lamivudine-based ART (3 ART-resistant and 3 ART-sensitive subjects with matching durations of ART) were subjected to comprehensive microarray expression profiling in order to screen out lncRNAs associated with ART sensitivity. Secondly, during the validation stage, promising lncRNAs were evaluated via a 1:4 matched case-control study using 50 subjects (10 ART-resistant and 40 ART-sensitive subjects with matching durations of ART). RESULTS: Seven lncRNAs were screened out (P < 1.06 × 10-3) in the first stage. Among these, two lncRNAs (n341598 and n407911) survived validation conducted at the second stage (n341598: P < 0.001; n407911: P = 0.007), while another lncRNA n406445 showed marginally significant (P = 0.049). All three showed higher expression in ART-resistant subjects compared to that in ART-sensitive subjects. The area under the ROC curve (AUC) for n341598 was 0.867 (95 % CI: 0.796-0.966; P < 0.001), which was better than that for n406445 (0.702) and n407911 (0.780). Meanwhile, the AUC for n341598 was better than that of any combination of the three lncRNAs. CONCLUSION: Our study identified three highly expressed lncRNAs in patients with HIV ART-resistant, among which the lncRNA n341598 may be utilized as an optimal biomarker to distinguish ART-resistant and ART-sensitive patients. Further studies aimed at revealing the molecular mechanisms underlying the regulation of ART sensitivity by n341598 are warranted to complement our findings.

Tetrandrine Treatment May Improve Clinical Outcome in Patients with COVID-19.

Background and objectives: The COVID-19 pandemic continues worldwide, and there is no effective treatment to treat it. Chinese medicine is considered the recommended treatment for COVID-19 in China. This study aimed to examine the effectiveness of tetrandrine in treating COVID-19, which is originally derived from Chinese medicine. Materials and Methods: A total of 60 patients, categorized into three types (mild, moderate, severe), from Daye Hospital of Chinese Medicine with a diagnosis of COVID-19 were included in this study. Demographics, medical history, treatment, and results were collected. We defined two main groups according to the clinical outcome between improvement and recovery. All underlying factors including clinical outcomes were assessed in the total number of COVID-19 patients and moderate-type patients. Results: In a total of 60 patients, there were significant differences in the clinical outcome underlying treatment with antibiotics, tetrandrine, and arbidol (p < 0.05). When the comparison was limited to the moderate type, treatment with tetrandrine further increased recovery rate (p = 0.007). However, the difference disappeared, and no association was indicated between the clinical outcome and the treatment with and without antibiotic (p = 0.224) and arbidol (p = 0.318) in the moderate-type patients. In all-type and moderate-type patients, tetrandrine improved the rate of improvement in cough and fatigue on day 7 (p < 0.05). Conclusions: Tetrandrine may improve clinical outcome in COVID-19 patientsand could be a promising potential natural antiviral agent for the prevention and treatment of COVID-19.

Novel Functional eQTL-SNPs Associated With Susceptibility to Mycoplasma pneumoniae Pneumonia in Children.

Background: The functional causal single-nucleotide polymorphisms (SNPs) associated with susceptibility to Mycoplasma pneumoniae Pneumonia (MPP) have scarcely been identified. In this study, we aimed to analyze the association between the functional expression quantitative trait locus (eQTL)-SNPs and the risk of MPP. Methods: First, we identified reported genes associated with MPP from the human disease database, MalaCards. After investigating multiple databases, we systematically selected seven functional eQTL-SNPs (rs2070874, rs360720, rs8032531, rs4316, rs4353, rs7258241, and rs2250656). Finally, the selected eQTL-SNPs were genotyped using the TaqMan genotyping technology, and compared between 100 children with MPP and 178 healthy controls. Results: We found that three eQTL-SNPs (rs8032531 in CD276 and rs4316 and rs4353 in ACE) were significantly associated with susceptibility to MPP. Joint analysis of the three eQTL-SNPs revealed that the risk of MPP increased with an increase in the number of risk alleles present. Plasma protein expression levels of CD276 and ACE were distinctively higher in children with MPP than in healthy children (CD276: P < 0.001; ACE: P = 0.001). Conclusion: Functional eQTL-SNPs in CD276 and ACE may affect the susceptibility to MPP. The risk of developing MPP is higher in patients harboring a greater number of unfavorable alleles of the aforementioned SNPs.

A novel circRNA-SNP may increase susceptibility to silicosis.

In this study, we aimed to reveal the association between circRNA-related single nucleotide polymorphisms (SNPs) with the susceptibility of silicosis. To achieve this goal, a silicosis-related GWAS was constructed to select the candidate SNPs, and circBase database was utilized to select the promising SNPs which may locate on circRNAs. In addition, the eQTL analysis between the SNPs and located genes was performed to select the candidate SNPs. Finally, the association between candidate SNPs with the susceptibility of silicosis was validated. As a result, we firstly selected 10,922 SNPs with P < 1 × 10-3 through the silicosis-related GWAS. Among which, 1,752 SNPs were identified that may locate on 2,660 circRNAs. After the MAF evaluation and the sequences checking, we obtained 94 SNPs and related 105 circRNAs. EQTL analysis indicated that 7 circRNA-SNPs might regulate the expression of located genes. Subsequently, a strong association was found between variant A of rs17115143 and silicosis risk in the validation stage (OR= 1.68, P = 0.032). Combination of the GWAS data and Taqman genotyping data also revealed a strong association between rs17115143 and silicosis risk in both dominant and additive models (dom: OR= 1.96, P = 3.98 × 10-4; add: OR= 1.40, P = 3.06 × 10-4). In conclusion, the variant A allele of circRNA-SNP rs17115143 could be a risk factor in the progression of silicosis. And related 6 circRNAs may function as novel biomarkers for the diagnostic of silicosis. Further researches to explore the biological mechanisms of rs17115143 related 6 circRNAs in the regulation of silicosis are warranted.

Peripheral blood circular RNA hsa_circ_0058493 as a potential novel biomarker for silicosis and idiopathic pulmonary fibrosis.

Existing studies reported that some circular RNAs (circRNAs) play vital roles in the development of pulmonary fibrosis. However, few studies explored the biomarker potential of circRNAs for pulmonary fibrosis based on population data. Therefore, we aimed to identify peripheral blood circRNAs as potential biomarkers for diagnosing silicosis and idiopathic pulmonary fibrosis (IPF). In brief, an RNA-seq screening based on 4 silicosis cases and 4 controls was initially performed. Differentially expressed circRNAs were combined with the human serum circRNA dataset to identify overlapping serum-detectable circRNAs, followed by validation using the GEO dataset (3 IPF cases and 3 controls) and subsequent qRT-PCR, including 84 additional individuals. Following the above steps, 243 differentially expressed circRNAs were identified during the screening stage, with fold changes ≥ 1.5 and P < 0.05. Of note, the human serum circRNA dataset encompassed 28 of 243 circRNAs. GEO (GSE102660) validation revealed two highly expressed circRNAs (P < 0.05) in the IPF case group. Furthermore, at the enlarged sample validation stage, hsa_circ_0058493 was highly expressed in both silicosis and IPF cases (silicosis: P = 1.16 × 10-6; IPF: P = 7.46 × 10-5). Additionally, hsa_circ_0058493 expression was significantly increased in MRC-5 cells upon TGF-ß1 treatment, while hsa_circ_0058493 knockdown inhibited the expression of fibrotic molecules by affecting the epithelial-mesenchymal transition process. These shreds of evidence indicated that hsa_circ_0058493 might serve as a novel biomarker for diagnosing silicosis and IPF.