Forkhead O Transcription Factor 4 Restricts HBV Covalently Closed Circular DNA Transcription and HBV Replication through Genetic Downregulation of Hepatocyte Nuclear Factor 4 Alpha and Epigenetic Suppression of Covalently Closed Circular DNA via Interacting with Promyelocytic Leukemia Protein.

Nuclear located hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) remains the key obstacle to cure chronic hepatitis B (CHB). In our previous investigation, it was found that FoxO4 could inhibit HBV core promoter activity through downregulating the expression of HNF4α. However, the exact mechanisms whereby FoxO4 inhibits HBV replication, especially its effect on cccDNA, remain unclear. Here, our data further revealed that FoxO4 could effectively inhibit cccDNA mediated transcription and HBV replication without affecting cccDNA level. Mechanistic study showed that FoxO4 could cause epigenetic suppression of cccDNA. Although FoxO4-mediated downregulation of HNF4α contributed to inhibiting HBV core promoter activity, it had little effect on cccDNA epigenetic regulation. Further, it was found that FoxO4 could colocalize within promyelocytic leukemia protein (PML) nuclear bodies and interact with PML. Of note, PML was revealed to be critical for FoxO4-mediated inhibition of cccDNA epigenetic modification and of the following cccDNA transcription and HBV replication. Furthermore, FoxO4 was found to be downregulated in HBV-infected hepatocytes and human liver tissues, and it was negatively correlated with cccDNA transcriptional activity in CHB patients. Together, these findings highlight the role of FoxO4 in suppressing cccDNA transcription and HBV replication via genetic downregulation of HNF4α and epigenetic suppression of cccDNA through interacting with PML. Targeting FoxO4 may present as a new therapeutic strategy against chronic HBV infection. IMPORTANCE HBV cccDNA is a determining factor for viral persistence and the main obstacle for a cure of chronic hepatitis B. Strategies that target cccDNA directly are therefore of great importance in controlling persistent HBV infection. In present investigation, we found that FoxO4 could efficiently suppress cccDNA transcription and HBV replication without affecting the level of cccDNA itself. Further, our data revealed that FoxO4 might inhibit cccDNA function via a two-part mechanism: one is to epigenetically suppress cccDNA transcription via interacting with PML, and the other is to inhibit HBV core promoter activity via the genetic downregulation of HNF4α. Of note, HBV might dampen the expression of FoxO4 for its own persistent infection. We propose that manipulation of FoxO4 may present as a potential therapeutic strategy against chronic HBV infection.

The trajectories and associations of insomnia symptoms with addictive behaviours in adolescents: A two-year longitudinal study.

Insomnia displays heterogeneous trajectories across adolescence, which may induce addictive behaviours, including internet gaming disorder and substance use. This study aimed to investigate the latent trajectory classes of insomnia symptoms over 2 years and to examine the associations between insomnia trajectories and these addictive behaviours. Participants were 910 adolescents from six middle schools in Shanghai, China (52.7% males; mean age = 13.17 years). The three-wave survey measured insomnia symptoms, internet gaming disorder, substance use, depressive symptoms, and sociodemographic characteristics from 7th to 9th grade. Latent class growth modelling was performed to identify the latent trajectory classes of insomnia symptoms. Then multivariable logistic regressions were conducted within the best-fitting latent class growth model to examine the associations of insomnia trajectories with internet gaming disorder and substance use. Two latent trajectory classes of insomnia symptoms were recognised: the non-insomnia group (71.8%) and the insomnia group (28.2%). In the multivariable analysis controlling for baseline demographic variables and depressive symptoms, the insomnia group had a higher risk of developing internet gaming disorder (OR = 2.203 [95% CI: 1.258-3.858]) and substance use (OR = 2.215 [95% CI: 1.324-3.705]) compared with the non-insomnia group. These findings add to a growing body of research on heterogeneous trajectories of insomnia symptoms during adolescence, suggesting that intervention strategies are needed to target the characteristics or developmental patterns of different insomnia subgroups. The ultimate goal is to mitigate the impact of insomnia symptoms on adolescent addictive behaviours.

The role of sexual compulsivity in unprotected intercourse among STI patients in Shanghai, China.

BACKGROUND: Sexual compulsivity (SC) and its relationship with unprotected intercourse (UI) have long been an intriguing topic, but its existential meaning in the management of public health or, more precisely, sexually transmitted infections (STIs) has rarely been studied to date. This study examines whether SC plays a role in UI among sexually active STI patients. METHOD: A cross-sectional study was conducted in two sexual transmitted disease (STD) clinicals of Shanghai Skin Diseases Hospital in Shanghai. Totally 664 sexually active STI patients were included. RESULTS: The ages of the 664 participants ranged from 18 to 76 years, with 58.73% between 26 and 40 years old. 449 (191 male and 258 female) reported had UI during the past 6 months. Although the only statistically significant difference (p < 0.01) was in relation to UI with a casual sexual partner, the difference between male/female and regular/casual sexual partners remained evident. CONCLUSIONS: SC is evidently a potential predictor of UI with a casual sexual partner in male STI patients, while the use of condoms is more likely to be affected by other factors. In addition to general sexual education, counseling interventions should be provided by health institutions, and specific intervention methods targeting gender and sexual partners should be considered.

Longitudinal predictors for incidence of internet gaming disorder among adolescents: The roles of time spent on gaming and depressive symptoms.

INTRODUCTION: Internet gaming disorder (IGD) was popular among adolescents worldwide, but whether some associated factors could contribute to the development of IGD was unclear. This longitudinal study explored the temporal stability of IGD over one year and determined the predictors for IGD incidence. METHODS: Participants were 1121 adolescents from six junior high schools in Shanghai, China (50.6% males; median age = 13.0 years). The baseline and follow-up questionnaire survey measured IGD, time spent on gaming, depressive symptoms, insomnia condition, substance use and background variables from 7th to 8th grade. Multivariate logistic regression analysis was conducted to test the associations between other factors and IGD incidence. RESULTS: IGD incidence was 7.7% at one-year follow-up. Gender, family financial condition, parental educational level, time spent on gaming, insomnia condition and depressive symptoms were associated with IGD incidence in univariate analysis, whereas only gender, family financial condition, time spent on gaming and depressive symptoms were associated with IGD incidence in multivariate logistic regression. CONCLUSIONS: IGD might persist for years during adolescence. After controlling for sociodemographic factors, time spent on gaming and depressive symptoms were independent predictors for IGD incidence.

Characteristics of within-household varicella transmission events associated with school outbreaks in Shanghai, China, 2009-2018.

Transmission of varicella occurs frequently in schools and households. We investigated the characteristics of varicella cases derived from within-household transmission and the modes of varicella transmission between school and household settings in Shanghai, China, from 2009 to 2018. Within-household transmission occurred in 278 households, of which 134 transmission events were between children. Sixty-one household varicella transmission events may be attributed to isolation procedures for infected students during school outbreaks, and 7.6% of school outbreaks were caused by schoolchildren cases derived from within-household transmission. The frequency of 'school-household-school' transmission adds an additional layer of complexity to the control of school varicella outbreaks. Administration of varicella vaccine as post-exposure prophylaxis after exposure is considered to be an effective measure to control varicella spread within households and schools.

Psychosocial Syndemic of suicidal ideation: a cross-sectional study among sexually transmitted infection patients in Shanghai, China.

BACKGROUND: Patients with sexually transmitted infections (STIs) experience difficulties with stability and trust in long-term relationships and have poor mental health, factors that may lead to suicidal ideation. We sought to verify whether psychosocial health problems among patients with STIs were associated with these patients' suicidal ideation and to examine the syndemic effect of multiple psychosocial problems on suicidal ideation. METHODS: This was a cross-sectional study of 519 STI patients at the Shanghai Skin Disease Hospital. Demographic, psychosocial, and suicidal ideation information about the participants was collected by questionnaire. Logistic regressions were performed to detect the association between demographic variables and suicidal ideation, as well as each individual psychosocial variable and suicidal ideation, and to verify the syndemic effect of psychosocial factors. RESULTS: Of the participants, 25.0% (130/519) reported having suicidal ideation. In univariable analysis, low self-esteem, loneliness, depression, entrapment, defeat, and unsatisfied interpersonal needs were associated with suicidal ideation. Multivariable analysis found depression (odds ratio [OR]: 4.1; 95% confidence interval [CI]: 2.3-7.2) and entrapment (OR: 2.1; 95%CI: 1.1-4.1) each had a more significant relation with suicidal ideation than the other psychosocial problems examined. STI patients who experienced two or more psychosocial health problems had approximately fourfold odds of suicide ideation (adjusted OR [AOR]: 4.2; 95%CI: 2.6-6.8) compared with those in the non-syndemic group, especially in the high-level (five or more psychosocial problems) group (AOR: 7.0; 95%CI: 3.9-12.5). CONCLUSIONS: The study found the participants had a high rate of suicidal ideation and suffered from severe psychosocial problems. These results show a syndemic effect of psychosocial problems on increasing the odds of suicidal ideation. Our findings suggest an urgent need for efforts to prevent suicidal ideation among STI patients toward improving the social and health conditions of this population.

TUSC2P suppresses the tumor function of esophageal squamous cell carcinoma by regulating TUSC2 expression and correlates with disease prognosis.

BACKGROUND: Pseudogenes are RNA transcripts with high homology with its parent protein-coding genes. Although pseudogenes lost the ability to produce protein, it still exert import biological function, and play important role in the pathogenesis of a wide varity of tumors; However, the role of pseudogenes in esophageal squamous cell carcinoma (ESCC) is poorly understood. METHODS: TUSC2P function in ESCC were explored using both in vitro and in vivo experiments cell proliferation, invasion and apoptosis assay was performed to evaluated the effect of TUSC2P on the tumor biology of ESCC. Expression of relative genes was assessed by quantitative real-time PCR (qRT-PCR) and western blotting in EC109 and TE-1 cell, as well as ESCC patients. 3'UTR luciferase assay was used to confirm the direct binding of miRNAs with TUSC2 and TUSC2P 3'UTR. Relation betweenTUSC2P, TUSC2 and ESCC prognosis was predicted by survival analysis (n = 56). RESULTS: Pseudogene TUSC2P was down regulated in ESCC tissues compared with paired normal adjacent tissues, and the expression of TUSC2P was significantly correlated with survivalof ESCC patients. Over expression of TUSC2P in EC109 and TE-1 cells resulted in altered expression of TUSC2, thus inhibited proliferation, invasion and promoted apoptosis. Dual luciferase assay demonstrated that TUSC2P 3'UTR decoyed miR-17-5p, miR-520a-3p, miR-608, miR-661 from binding to TUSC2. CONCLUSIONS: TUSC2P can suppresses the tumor function of esophageal squamous cell carcinoma by regulating TUSC2 expression and may also serve as a prognostic factor for ESCC patients.

MiRNA-17 encoded by the miR-17-92 cluster increases the potential for steatosis in hepatoma cells by targeting CYP7A1.

BACKGROUND: The miRNA cluster miR-17-92 is known to act as an oncogene in various cancers. Members of this cluster were also found to be involved in some other pathological process, such as steatosis, which is a pivotal event in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether miR-17, one of the most functional miRNAs in the miR-17-92 family, participates in the process of steatosis in hepatoma cells. METHODS: We developed both a miR-17-expressing transgenic mouse model and a miR-17-expressing HepG2 cell model, the latter was established via stable transfection. Real-time PCR and western blot were applied to measure the expression levels of miR-17 and the potential target gene CYP7A1. The luciferase assay was used to confirm direct binding of miR-17 and CYP7A1. The oleic acid induction assay and Oil-Red-O staining were performed to support the determination of steatotic changes in HepG2 cell. RESULTS: Extensive steatotic changes were observed in the livers of transgenic mice. Fewer were seen in the wild-type animals. CYP7A1 was confirmed as a target gene of miR-17, and the expression of CYP7A1 was found to be negatively regulated in both the transgenic mice liver cells and the miR-17-expressing HepG2 cells. CYP7A1 was found to participate in miR-17-induced steatosis, as its repressed expression in miR-17 HepG2 cells exacerbated steatotic change. Re-introduction of CYP7A1 into miR-17 HepG2 cell partially alleviated steatosis. CONCLUSIONS: miR-17 is a novel regulator of CYP7A1 signaling in hepatic lipid metabolism, suggesting a potential therapeutic approach for fatty liver.

Perceived entrapment predicts first-onset suicidal ideation: A longitudinal study among medical students in China.

Introduction: The prevalence of suicidal ideation among medical students is high. Evidence indicates that feelings of entrapment are a predictor of suicidal ideation. In this study, we aimed to (1) investigate the prevalence of first-onset suicidal ideation among Chinese medical students and (2) explore the predictive effects of perceived entrapment on first-onset suicidal ideation. Methods: This longitudinal study was conducted between 2018 and 2019 among 211 newly enrolled medical students in Shanghai. Using an anonymous questionnaire, we collected information on sociodemographic (sex, major, parents' income, and academic performance) and psychological (entrapment, depression, loneliness, defeat, social support, and interpersonal needs) variables as well as suicidal ideation. Participants were divided into four subgroups based on their exposure to entrapment (control, new-onset, reduced, and persistent). The primary outcome, first-onset suicidal ideation, was defined as suicidal ideation absent at baseline but present at follow-up. Results: In total, 54.98% of participants (116/211) were women, and 76.78% (162/211) majored in clinical medicine. In the follow-up survey, 6.16% of participants (16/211) reported first-onset suicidal ideation, 17.54% (37/211) reported new-onset entrapment, and 12.80% (27/211) reported persistent entrapment during follow-up. Compared with the control group who reported no perceived entrapment at baseline and follow-up, participants who reported new-onset entrapment had the highest risk of new-onset suicidal ideation [odds ratio (OR) = 14.700, 95% confidence interval (CI) = 2.906-74.364; adjusted OR = 8.798; 95% CI = 1.588-48.757; multivariate OR = 8.238, 95% CI = 1.394-48.693). Conclusion: New-onset entrapment can significantly predict suicidal ideation. Therefore, greater attention is needed for new-onset entrapment, such as intervention for suicidal ideation.

Social exclusion, thwarted belongingness, and perceived burdensomeness: construct validity and psychometric properties of the Interpersonal Needs Questionnaire among patients with sexually transmitted infections in Shanghai, China.

BACKGROUND: Sexually transmitted infections (STIs) are a serious public health problem worldwide. Patients with STIs have a high rate of psychosocial problems and may perceive unmet interpersonal needs, which is considered a proximal and sufficient cause of suicidal thoughts and behaviors. The present study examined the construct validity and psychometric properties of the 15-item Interpersonal Needs Questionnaire among patients with STIs in Shanghai, China. METHODS: We recruited 910 patients with STIs (438 males and 472 females; mean age = 38.72, standard deviation [SD] = 13.034) from the Shanghai Skin Disease Hospital using accidental sampling. Baseline descriptive statistics were calculated using R 4.0.0, and a latent variable model was developed using Mplus 7.4. RESULTS: The construct validity results supported a latent variable measurement model with three distinct but related constructs (thwarted belongingness, perceived burdensomeness, and social exclusion) (p < 0.001, χ2/df = 2.475, root mean square error of approximation = 0.057, comparative fit index = 0.931, Tucker-Lewis index = 0.916, standardized root mean residual = 0.044). The Cronbach's α and McDonald's ω values were 0.849 and 0.767 for the total scale, 0.888 and 0.889 for perceived burdensomeness, 0.764 and 0.777 for social exclusion, and 0.892 and 0.893 for thwarted belongingness. Interpersonal needs were significantly associated with low self-esteem (r = 0.539), loneliness (r = 0.573), depression (r = 0.338), entrapment (r = 0.420), defeat (r = 0.579), and low perceived social support (r = 0.424). CONCLUSIONS: This was the first study to highlight social exclusion as a distinct but related dimension of interpersonal needs. This finding indicates that patients with STIs perceive high social exclusion. Therefore, health providers should consider the psychological status of these patients and implement strategies to support their integration into society.

STING signaling activation inhibits HBV replication and attenuates the severity of liver injury and HBV-induced fibrosis.

The covalently closed circular DNA (cccDNA) of HBV plays a crucial role in viral persistence and is also a risk factor for developing HBV-induced diseases, including liver fibrosis. Stimulator of interferon genes (STING), a master regulator of DNA-mediated innate immune activation, is a potential therapeutic target for viral infection and virus-related diseases. In this study, agonist-induced STING signaling activation in macrophages was revealed to inhibit cccDNA-mediated transcription and HBV replication via epigenetic modification in hepatocytes. Notably, STING activation could efficiently attenuate the severity of liver injury and fibrosis in a chronic recombinant cccDNA (rcccDNA) mouse model, which is a proven suitable research platform for HBV-induced fibrosis. Mechanistically, STING-activated autophagic flux could suppress macrophage inflammasome activation, leading to the amelioration of liver injury and HBV-induced fibrosis. Overall, the activation of STING signaling could inhibit HBV replication through epigenetic suppression of cccDNA and alleviate HBV-induced liver fibrosis through the suppression of macrophage inflammasome activation by activating autophagic flux in a chronic HBV mouse model. This study suggests that targeting the STING signaling pathway may be an important therapeutic strategy to protect against persistent HBV replication and HBV-induced fibrosis.

Pre-Exposure Prophylaxis (PrEP) Adherence Questionnaire: Psychometric Validation among Sexually Transmitted Infection Patients in China.

BACKGROUND: Ensuring adherence guarantees the efficacy of pre-exposure prophylaxis (PrEP). METHODS: We conducted a cross-sectional study among 816 sexually transmitted infection (STI) patients in Shanghai. The questionnaire included self-reported demographic characteristics, self-administered items on adherence to free oral PrEP, and PrEP uptake behavior measurement. We conducted item analysis, reliability analysis, validity analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Not all items were considered acceptable in the item analysis. The questionnaire had a McDonald's ω coefficient of 0.847. The scale-level content validity index (CVI) was 0.938 and the item-level CVI of each item ranged from 0.750 to 1. In exploratory factor analysis, we introduced a four-factor model accounting for 79.838% of the aggregate variance, which was validated in confirmatory factor analysis. Adding PrEP adherence questionnaire scores contributed to prediction of PrEP uptake behavior (p < 0.001) in regression analysis. The maximum area under the ROC curve was 0.778 (95% IC: 0.739-0.817). CONCLUSION: The PrEP adherence questionnaire presented psychometric validation among STI patients.

Prediction Model for COVID-19 Vaccination Intention among the Mobile Population in China: Validation and Stability.

Since China's launch of the COVID-19 vaccination, the situation of the public, especially the mobile population, has not been optimistic. We investigated 782 factory workers for whether they would get a COVID-19 vaccine within the next 6 months. The participants were divided into a training set and a testing set for external validation conformed to a ratio of 3:1 with R software. The variables were screened by the Lead Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Then, the prediction model, including important variables, used a multivariate logistic regression analysis and presented as a nomogram. The Receiver Operating Characteristic (ROC) curve, Kolmogorov-Smirnov (K-S) test, Lift test and Population Stability Index (PSI) were performed to test the validity and stability of the model and summarize the validation results. Only 45.54% of the participants had vaccination intentions, while 339 (43.35%) were unsure. Four of the 16 screened variables-self-efficacy, risk perception, perceived support and capability-were included in the prediction model. The results indicated that the model has a high predictive power and is highly stable. The government should be in the leading position, and the whole society should be mobilized and also make full use of peer education during vaccination initiatives.

The Impact of Social Network Site Addiction on Depression in Chinese Medical Students: A Serial Multiple Mediator Model Involving Loneliness and Unmet Interpersonal Needs.

The use of social network sites (SNSs) is inevitable in daily life. Everyone is likely to be addicted to SNSs, especially medical students. This study is aimed to assess the degree of SNS addiction and its relation to psychosocial factors such as depression, loneliness and unmet interpersonal needs among Chinese medical students. The cross-section survey was conducted from March to May in 2018 in Shanghai Jiao Tong University School of Medicine. Of the total 1067 participants, 33.18% had an SNS addiction, 87.7% of the participants used SNSs every day during last month and 53.42% of the participants used SNSs for at least an hour per day during the last week. SNS addiction is positively related with depression both directly and indirectly. The mediating roles of loneliness and unmet interpersonal needs on the relationship between SNS addiction and depression are significant. For the well-being of medical students, efforts should be taken to prevent them from becoming addicted to SNSs.

Regulation of Molecular Chaperone GRP78 by Hepatitis B Virus: Control of Viral Replication and Cell Survival.

Chronic hepatitis B (CHB) remains a global health problem, carrying a high risk for progression into cirrhosis and liver failure. Molecular chaperones are involved in diverse pathophysiological processes including viral infection. However, the role of molecular chaperones in hepatitis B virus (HBV) infection and its underlying mechanisms remain unclear. Here, we identified GRP78 as one of the molecular chaperones most strongly induced by HBV in human hepatocytes. Gain- and loss-of-function analyses demonstrated that GRP78 exerted an inhibitory effect on HBV transcription and replication. Further study showed that GRP78 was involved in the activation of AKT/mTOR signaling in hepatocytes, which contributed to GRP78-mediated inhibition of HBV. Of note, HBV-upregulated GRP78 was found to play a crucial role in maintaining the survival of hepatocytes via facilitating a mild endoplasmic reticulum (ER) stress. Together, our findings suggest that HBV may sacrifice part of its replication for establishing a persistent infection through induction of GRP78, a master ER stress regulator. Targeting GRP78 may help develop to design novel therapeutic strategies against chronic HBV infection and the associated hepatocellular carcinoma.

The lncRNA ENST00000608794 acts as a competing endogenous RNA to regulate PDK4 expression by sponging miR-15b-5p in dexamethasone induced steatosis.

The contribution of ncRNAs, especially long non-coding RNAs (lncRNAs) to drug induced steatosis remains largely unknown. The aim of this study was to investigate the role of lncRNA ENST00000608794 in dexamethasone induced steatosis. We found that ENST00000608794 is expressed at higher levels in dexamethasone treated HepG2 cell, and ENST00000608794 can bind and be regulated by miR-15b-5p. Ectopic expression of ENST00000608794 enhanced steatosis and the protein expression of PDK4 which is a critical gene in lipid metabolism and also is a target of miR-15b-5p. However, the differentiated PDK4 expression between control and ectopic expression of ENST00000608794 was absence in the presence of miR-15b-5p inhibitor. Moreover, in dexamethasone treated HepG2 cell lines, ENST00000608794 increased whether with miR-15b-5p inhibitor treatment or not, while increase of PDK4 expression by dexamethasone was greatly compromised in the presence of miR-15b-5p mimic. Meanwhile, dexamethasone induced steatosis could be ameliorated by silencing ENST00000608794 or expressing miR-15b-5p. Taken together, the results suggested that ENST00000608794 plays an important role in dexamethasone induced steatosis, which was partly mediated by derepressing of PDK4 through competitively binding to miR-15b-5p.

Nrf2-regulated miR-380-3p Blocks the Translation of Sp3 Protein and Its Mediation of Paraquat-Induced Toxicity in Mouse Neuroblastoma N2a Cells.

Laboratorial and epidemiological research has established a relationship between paraquat (PQ) exposure and a risk for Parkinson's disease. Previously, we have investigated the effects of nuclear factor erythroid 2 related factor 2 (Nrf2) and microRNAs in PQ-induced neurotoxicity, addressing the function of miR-380-3p, a microRNA dysregulated by PQ, as well as Nrf2 deficiency. Nrf2 is known to mediate the expression of a variety of genes, including noncoding genes. By chromatin immunoprecipitation, we identified the relationship between Nrf2 and miR-380-3p in transcriptional regulation. qRT-PCR, Western blots, and dual-luciferase reporter gene assay showed that miR-380-3p blocked the translation of the transcription factor specificity protein-3 (Sp3) in the absence of degradation of Sp3 mRNA. Results based on cell counting analysis, annexin v-fluorescein isothiocyanate/propidium iodide double-staining assay, and propidium iodide staining showed that overexpression of miR-380-3p inhibited cell proliferation, increased the apoptotic rate, induced cell cycle arrest, and intensified the toxicity of PQ in mouse neuroblastoma (N2a [Neuro2a]) cells. Knockdown of Sp3 inhibited cell proliferation and eclipsed the alterations induced by miR-380-3p in cell proliferation. Two mediators of apoptosis and cell cycle identified in previous studies as Sp3-regulated, namely cyclin-dependent kinase inhibitor 1 (p21) and calmodulin (CaM), were dysregulated by PQ, but not Sp3 deficiency. In conclusion, Nrf2-regulated miR-380-3p inhibited cell proliferation and enhanced the PQ-induced toxicity in N2a cells potentially by blocking the translation Sp3 mRNA. We conclude that CaM and p21 were involved in PQ-induced toxicity.

The expression profiling and ontology analysis of non-coding RNAs in dexamethasone induced steatosis in hepatoma cell.

Increasing amounts of evidence have indicated that non-coding RNAs (ncRNAs) have important regulatory potential in various biological processes. However, the contribution of ncRNAs, especially long non-coding RNAs (lncRNAs) to drug induced steatosis remain largely unknown. The aim of this study is to investigate miRNA, lncRNA and mRNA expression profiles and their potential roles in the process of drug induced steatosis. Microarray expression profiles of miRNAs, lncRNAs and mRNAs were determined in dexamethasone treated HepG2 cell as well as control cell. Differential expression, pathway and gene network analyses were developed to identify possible functional RNA molecules in dexamethasone induced steatosis. Compared with control HepG2 cell, 652 lncRNAs (528 up-regulated and 124 down-regulated), 655 mRNAs (527 upregulated and 128 down-regulated) and 114 miRNAs (55 miRNAs up-regulated and 59 down-regulated) were differentially expressed in dexamethasone treated HepG2 cell. Pathway analysis showed that the fatty acid biosynthesis, insulin resistance, PPAR signaling pathway, regulation of lipolysis in adipocytes, carbohydrate digestion and absorption, steroid hormone biosynthesis signaling pathways had a close relationship with dexamethasone induced steatosis. 10 highly dysregulated mRNAs and 20 miRNAs, which are closely related to lipid metabolism, were identified and validated by PCR, which followed by ceRNA analysis. CeRNA network analysis identified 5 lipid metabolism related genes, including CYP7A1, CYP11A1, PDK4, ABHD5, ACSL1. It also identified 12 miRNAs (miR-23a-3p, miR-519d-3p, miR-4328, miR-15b-5p etc.) and 177 lncRNAs (ENST00000508884, ENST00000608794, ENST00000568457 etc.). Our results provide a foundation and an expansive view of the roles and mechanisms of ncRNAs in dexamethasone induced steatosis.