Blood transfusion is correlated with elevated adult all-cause mortality and cardiovascular mortality in the United States: NHANES 1999 to 2018 population-based matched propensity score study.

BACKGROUND AND AIMS: The association of blood transfusion with an increase in medium- and short-term mortality in specific populations has been confirmed. However, the correlation between blood transfusion and long-term mortality in the general population remains unclear. This cohort study evaluated the correlation between blood transfusion and overall and cause-specific mortality in the general American adult population. METHODS: The authors utilized 10 sets of 2-year cycle data (1999-2018) from the National Health and Nutrition Examination Survey on the outcomes of adults who did and did not receive blood transfusions. Propensity score-matching (1:1) was performed based on age, sex, race, education level, marital status, poverty-income ratio, arteriosclerotic cardiovascular disease, cancer, anemia, hypertension, and diabetes status. After controlling for demographic characteristics and clinical risk factors, Cox regression analysis was performed to evaluate the correlation between blood transfusion and all-cause and cause-specific mortality. RESULTS: The study included 48,004 adult participants. The risk of all-cause mortality increased by 101 % with blood transfusion, and the risk of cardiovascular mortality increased by 165 %. After propensity score-matching, 6,116 pairs of cases were retained, and the risk of all-cause mortality increased by 84 % with blood transfusion, and the risk of cardiovascular mortality increased by 137 %. The sensitivity analysis results were robust. CONCLUSIONS: In the general American population, blood transfusion significantly impacts long-term all-cause and cardiovascular mortality and may be an unacknowledged risk factor for death. Thus, the effective management of blood transfusion in the general population may be beneficial.

Paediatric off-label use of drugs in Gansu, China: a multicentre cross-sectional study.

OBJECTIVE: To examine the current prevalence and cost of paediatric off-label drug prescriptions in Gansu, China, and the potential influencing factors. DESIGN: The prevalence of off-label prescriptions in paediatrics was evaluated according to the National Medical Products Administration drug instructions in the China Pharmaceutical Reference (China Pharmaceutical Reference, MCDEX) database. The evidence of the prescription was determined by existing clinical practice guidelines and the Thomson Grade in the Micromedex 2021 compendium. We used logistic regression to investigate the characteristics that influence paediatric off-label drug use after single-factor regression analysis. SETTING: A multicentre cross-sectional study of outpatient paediatric prescriptions in 196 secondary and tertiary hospitals in Gansu Province, China, in March and September 2020. RESULTS: We retrieved 104 029 paediatric prescriptions, of which 39 480 (38.0%) contained off-label use. The most common diseases treated by off-label drugs were respiratory system diseases (n=15 831, 40.1%). A quarter of off-label prescriptions had adequate evidence basis (n=10 130, 25.6%). Unapproved indications were the most common type of off-label drug use (n=25 891, 65.6%). A total of 1177 different drugs were prescribed off-label, with multienzyme tablets being the most common drug (n=1790, 3.5%). The total cost of the prescribed off-label drugs was ¥106 116/day. Off-label prescriptions were less frequent in tertiary than in secondary hospitals. Topical preparations were more commonly prescribed off-label than other types of drugs. Senior-level clinicians prescribed drugs off-label more often than intermediate and junior clinicians. CONCLUSION: Off-label drug use is widespread in paediatric practice in China. Three-quarters of the prescriptions may potentially include inappropriate medication use, resulting in a daily economic burden of about ¥81 000 in 2020 in Gansu Province with 25 million inhabitants. The management of off-label drug use in paediatrics in China needs improvement.

Pharmacokinetics, Pharmacodynamics, and Safety of Single Dose HSK7653 Tablets in Chinese Subjects with Normal or Impaired Renal Function.

OBJECTIVE: HSK7653 is a novel, ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, promising for type 2 diabetes mellitus with a dosing regimen of once every 2 weeks. This trial investigates the pharmacokinetics (PKs), pharmacodynamics (PDs),and safety of HSK7653 in outpatients with normal or impaired renal function. METHODS: This is a multicenter, open-label, nonrandomized, parallel-controlled phase I clinical study that investigates the pharmacokinetic profiles of HSK7653 after a single oral administration in 42 subjects with mild (n = 8), moderate (n = 10), severe renal impairment (n = 10), and end-stage renal disease (without dialysis, n = 5) compared with matched control subjects with normal renal function (n = 9). Safety was evaluated throughout the study, and the pharmacodynamic effects were assessed on the basis of a DPP-4 inhibition rate. RESULTS: HSK7653 exposure levels including the maximum plasma concentration (Cmax), area under the plasma concentration-time curve from zero to last time of quantifiable concentration (AUC0-t), and area under the plasma concentration-time curve from zero to infinity (AUC0-inf) showed no significant differences related to the severity of renal impairment. Renal clearance (CLR) showed a certain downtrend along with the severity of renal impairment. The CLR of the group with severe renal impairment and the group with end-stage renal disease were basically similar. The DPP-4 inhibition rate-time curve graph was similar among the renal function groups. All groups had favorable safety, and no serious adverse events occurred. CONCLUSIONS: HSK7653 is a potent oral DPP-4 inhibitor with a long plasma half-life, supporting a dosing regimen of once every 2 weeks. Impaired renal function does not appear to impact the pharmacokinetic and pharmacodynamic properties of HSK7653 after a single administration in Chinese subjects. HSK7653 is also well tolerated without an increase in adverse events with increasing renal impairment. These results indicate that dose adjustment of HSK7653 may not be required in patients with renal impairment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05497297.

m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR.

The pathologic significance of the circular RNA DDIT4 (circDDIT4), which is formed by backsplicing at the 3'-untranslated region (UTR) with a 5' splice acceptor site in exon 2 of linear DDIT4 mRNA, has yet to be determined. Our study found that circDDIT4 is downregulated in prostate cancer and functions as a tumor suppressor during prostate cancer progression. By competitively binding to ELAV-like RNA binding protein 1 (ELAVL1/HuR) through its 3'-UTR, circDDIT4 acts as a protein sponge to decrease the expression of prostate cancer-overexpressed anoctamin 7 (ANO7). This promotes prostate cancer cell apoptosis while inhibiting cell proliferation and metastasis. Furthermore, we discovered that N6-methyladenosine (m6A) modification facilitates the biogenesis of circDDIT4. The methyltransferase complex consisting of WTAP/METTL3/METTL14 increases the level of circDDIT4, while the RNA demethylase FTO decreases it. IMPLICATIONS: These findings suggest that abnormal cotranscriptional modification of m6A promotes prostate cancer initiation and progression via a circular RNA-protein-cell signaling network.

Association of serum uric acid with risk of stroke in US adults: A cross-sectional study from NHANES 1999-2020.

BACKGROUND AND AIMS: The validity of high uric acid levels as an independent cause of stroke remains controversial, and the association between its low concentration and stroke is unclear. This study determines how different serum uric acid (SUA) levels are associated with stroke risk. METHODS: This cross-sectional study used continuous National Health and Nutrition Examination Survey data in the United States during 1999-2020. The SUA levels of 6.0, 6.8, and 9.0 mg/dL were all considered as cut-off points. Restricted cubic spline interpolation and logistic regression models were used to evaluate the different associations. Subgroup analyses and sensitivity analyses were conducted to evaluate the influence of multiple factors on the outcomes. RESULTS: The study included 23,413 participants aged ≥ 20 years. A J-shaped curve existed between SUA and stroke risk, and the risk of stroke was positively correlated with SUA levels in the overall population. Subgroup analysis of all adults in the SUA 6.8-9.0 mg/dL group showed that stroke risk for non-Hispanic white, obese, ex-smoker, and heavy drinking groups was increased, but for the other Hispanic group was reduced. In the SUA < 6.0 mg/dL group, stroke risk for ex-smoker, heavy drinkers, and no chronic kidney disease groups was increased. CONCLUSION: Our findings indicate a J-shaped relationship between SUA levels and stroke risk. Low and high SUA levels increased stroke risk for different populations, except in the other Hispanic population. Early SUA management is highly significant for stroke prevention in high-risk populations.

Can adding personalized rule-based feedback improve the therapeutic effect of self-help digital cognitive behavioral therapy for insomnia in young adults?

INTRODUCTION: Cognitive-behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for insomnia, but low accessibility and relatively high cost limits the dissemination of the treatment. Several forms of digital CBT-I have been developed to increase the accessibility and shown to be effective; however, the treatment effect may be restricted by the lack of interaction within the treatment. The current study examines whether the therapeutic effects of self-help digital CBT-I could be enhanced by adding simple rule-based personalized feedback. METHOD: Ninety-two young adults with self-reported insomnia were randomly assigned to three groups: a self-help group (SH, n = 31), who received an eight-session email-delivered CBT-I program; a feedback group (FB, n = 31), who went through the same CBT-I program with personalized feedback; and a waitlist group (WL, n = 30). The Insomnia Severity Index (ISI) was used as the primary outcome measure, and the 16-item version of the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16), Sleep Hygiene Practice Scale (SHPS), and sleep diary were used as the secondary outcome measures. Treatment satisfaction and adherence were also compared between the treatment groups. RESULTS: Both the SH and FB groups showed significantly more improvements in insomnia severity, sleep-related beliefs, and sleep hygiene behaviors than the WL group. Sleep onset latency and sleep efficiency in the sleep diary were also significantly improved after treatment. None of these effects significantly differed between the two treatment groups. Nonetheless, participants in the FB group reported higher treatment satisfaction than those in the SH group. CONCLUSION: This study supports the effectiveness of email-delivered self-help CBT-I for young adults with insomnia. Furthermore, while adding simple personalized feedback may not have an additional effect on sleep per se, it can enhance treatment satisfaction. This simple intervention shows promise in addressing sleep disturbance in young adults.

Identification of Long Noncoding RNAs That Exert Transcriptional Regulation by Forming RNA-DNA Triplexes in Prostate Cancer.

Long noncoding RNAs (lncRNAs) are involved in transcriptional regulation, and their deregulation is associated with the development of various human cancers, including prostate cancer (PCa). However, their underlying mechanisms remain unclear. In this study, lncRNAs that interact with DNA and regulate mRNA transcription in PCa were screened and identified to promote PCa development. First, 4195 protein-coding genes (PCGs, mRNAs) were obtained from the The Cancer Genome Atlas (TCGA) database, in which 1148 lncRNAs were differentially expressed in PCa. Then, 44,270 pairs of co-expression relationships were calculated between 612 lncRNAs and 2742 mRNAs, of which 42,596 (96%) were positively correlated. Among the 612 lncRNAs, 392 had the potential to interact with the promoter region to form DNA:DNA:RNA triplexes, from which lncRNA AD000684.2(AC002128.1) was selected for further validation. AC002128.1 was highly expressed in PCa. Furthermore, AD000684.2 positively regulated the expression of the correlated genes. In addition, AD000684.2 formed RNA-DNA triplexes with the promoter region of the regulated genes. Functional assays also demonstrated that lncRNA AD000684.2 promotes cell proliferation and motility, as well as inhibits apoptosis, in PCa cell lines. The results suggest that AD000684.2 could positively regulate the transcription of target genes via triplex structures and serve as a candidate prognostic biomarker and target for new therapies in human PCa.

Using New Peak Detection to Solve Sequence Variants Analysis Challenges in Bioprocess Development.

Recombinant therapeutic proteins have become the major class of drugs to treat various human diseases in recent years. Low levels of protein sequence variants (SVs) have been reported to be present in recombinant therapeutic proteins. The consequences of potential unwanted immune response from SVs of recombinant therapeutic proteins have increasingly drawn attention from regulatory authorities and the biopharmaceutical industry. It is highly desirable to detect low-level SVs during clone selection and early process development as part of the control strategy. Peptide mapping with LC-MS/MS analysis has been applied as a powerful tool to characterize post-translation modifications of therapeutic proteins. Despite the recent advancements in mass spectrometry hardware and software, it is still quite challenging and time-consuming to detect and identify low-level SVs. In this study, we present an optimized approach using new peak detection to detect and identify low level SVs with high confidence and high speed. The new approach makes sequence variants analysis by LC-MS/MS broadly applicable and practical in bioprocess development of therapeutic proteins.

Combined Ultrasound-Guided Thoracic Paravertebral Nerve Block with Subcostal Transversus Abdominis Plane Block for Analgesia After Total Minimally Invasive Mckeown Esophagectomy: A Randomized, Controlled, and Prospective Study.

INTRODUCTION: Thoracic paravertebral block (TPVB) and subcostal transverse abdominis plane block (TAP) have been considered to provide an effective analgesic effect for laparoscopic and thoracoscopic surgery, respectively. The purpose of this randomized, controlled, and prospective study was to evaluate the analgesic effect of TPVB combined with TAP in patients undergoing total minimally invasive Mckeown esophagectomy. METHODS: Between February 2020 and December 2021, a total of 168 esophageal cancer patients undergoing McKeown esophagectomy at the Cancer Center of Sun Yat-Sen University, China, were randomly assigned to receive patient-controlled epidural analgesia alone (group PCEA, n = 56), patient-controlled intravenous analgesia alone (group PCIA, n = 56), and TPVB combined with TAP and patient-controlled intravenous analgesia (group PVB, n = 56). The primary outcome was a visual analogue scale (VAS) pain score on movement 48 h postoperatively. Secondary endpoints were pain scores at other points, intervention-related side effects, surgical complications, and length of intensive care unit and hospital stay. For the VAS pain score, the Kruskal-Wallis method was conducted for comparison of 3 treatment groups and further pairwise comparison with Bonferroni correction. RESULTS: On movement, the VAS in the PVB group was higher than that in the PCEA group at 48 h, 72 h, 96 h, and 120 h postoperatively (p < 0.05) except in the postoperative anesthesia care unit (PACU) and 24 h postoperatively. The VAS in the PCIA group was higher than the PCEA and PVB groups in the first 4 days after surgery. The pulmonary complication rate in the PCIA group was significantly higher than the rate in the PCEA [95% Confidence Interval 0.214 (0.354, 0.067), p = 0.024]. CONCLUSIONS: Combined TPVB and TAP was more effective than intravenous opioid analgesia alone, while PCEA was more effective than TPVB combined with TAP and intravenous opioid analgesia for patients after McKeown esophagectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry; ChiCTR2000029588.

Androgen-Responsive Oncogenic lncRNA RP11-1023L17.1 Enhances c-Myc Protein Stability in Prostate Cancer.

Long noncoding RNAs (lncRNAs) have been found as novel participants in the pathophysiology of prostate cancer (PCa), which is predominantly regulated by androgen and its receptor. The biological function of androgen-responsive lncRNAs remains poorly understood. Here, we identified that lncRNA RP11-1023L17.1, which is highly expressed in PCa. RP11-1023L17.1 expression, can be directly repressed by the androgen receptor in PCa cells. RP11-1023L17.1 depletion inhibited the proliferation, migration, and cell cycle progression, and promoted the apoptosis of PCa cells, indicating that RP11-1023L17.1 acts as an oncogene in PCa cells. Microarray results revealed that RP11-1023L17.1 depletion downregulated the c-Myc transcription signature in PCa cells. RP11-1023L17.1 depletion-induced cellular phenotypes can be overcome by ectopically overexpressed c-Myc. Mechanistically, RP11-1023L17.1 represses FBXO32 mRNA expression, thereby enhancing c-Myc protein stability by blocking FBXO32-mediated c-Myc degradation. Our findings reveal the previously unrecognized roles of RP11-1023L17.1 in c-Myc-dependent PCa tumorigenesis.

AC016745.3 Regulates the Transcription of AR Target Genes by Antagonizing NONO.

The androgen receptor (AR) and its related signaling pathways play an important role in the development of prostate cancer (PCa). Long non-coding RNAs (lncRNAs) are involved in the regulation of tumorigenesis and development, but their specific mechanism of action remains unclear. This study examines the function and mechanisms of action of lncRNA AC016745.3 in the development of PCa. It shows that dihydrotestosterone (DHT) results in the AR-dependent suppression of AC016745.3 expression in the LNCaP androgen-sensitive human prostate adenocarcinoma cell line. In addition, overexpression of AC016745.3 inhibits the proliferation and migration of PCa cells, and suppresses the expression of AR target genes. This research also demonstrates that the protein NONO interacts with AR and functions as an AR co-activator, promoting AR transcriptional activity. Furthermore, using RNA immunoprecipitation (RIP)-PCR experiments, the study demonstrates that both NONO and AR can bind AC016745.3. Moreover, cell phenotypic experiments reveal that NONO can promote cellular proliferation and migration, and that AC016745.3 can partially antagonize the pro-oncogenic functions of NONO in PCa cells. In summary, the results indicate that AC016745.3 can bind NONO, suppressing its ability to promote AR-dependent transcriptional activity. Furthermore, DHT-dependent suppression of AC016745.3 expression can enhance NONO's promotion effect on AR.

Comprehensive Characterization of Androgen-Responsive circRNAs in Prostate Cancer.

The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5' to 3' polarity or 3' poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear. In this study, we identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs after dihydrotestosterone (DHT) stimulation using microarray. Among them, the expression of 1296 androgen-responsive circRNAs was consistent with that of their parent genes, and we thought AR might regulate the expression of these circRNAs at the transcriptional level. In addition, 1941 circRNAs expression was not consistent with their parent genes, and we speculated that AR may regulate the expression of those circRNAs at the posttranscriptional level through affecting alternative splicing. Analyzing the androgen-responsive circRNAs regulated at the posttranscriptional level, we identified two key RNA binding proteins (RBPs), WTAP and TNRC6, using the circInteractome database, which may play important role in the biogenesis of androgen-responsive circRNAs. Furthermore, we explored the potential biological functions and predicted the molecular mechanisms of two dysregulated circRNAs (circNFIA and circZNF561) in prostate cancer. In this study, we revealed that circNFIA was upregulated in prostate cancer tissues and plasma samples from patients with prostate cancer; circNFIA may play an oncogenic role in prostate cancer. In contrast, circZNF561 was downregulated and may act as a tumor suppressor in prostate cancer. Our results suggest that androgen-responsive circRNAs might regulate the progression of prostate cancer and could be novel diagnostic biomarkers.

A nomogram for predicting the risk of no-reflow after primary percutaneous coronary intervention in elderly patients with ST-segment elevation myocardial infarction.

BACKGROUND: The purpose of this study was to screen the predictive factors of no-reflow after a percutaneous coronary intervention (PCI) in elderly patients with ST-segment elevation myocardial infarction (STEMI), and to construct a nomogram model, to guide clinical treatment. METHODS: A total of 551 elderly STEMI patients (age >65) underwent direct PCI were randomly classified into training group (n=386, 70%) and validation group (n=165, 30%). All patients in the two groups were divided into a no-reflow group and a normal blood flow group according to whether there was a no-reflow phenomenon. Univariable and multivariable logistic regression analysis was used to analyze the relevant data, including demographic characteristics, clinical characteristics, coronary angiography results, electrocardiogram (ECG) results, and biochemical indicators. Then, a nomogram model was constructed on the screened risk factors. The performance of the nomogram was evaluated in terms of discrimination and calibration. The nomogram was further confirmed in the internal validation group. Additionally, decision curve analysis (DCA) was applied to assess the clinical usefulness of the nomogram. RESULTS: Five remarkable risk factors were determined: preoperative TIMI blood flow, the diameter of the target lesion, collateral circulation, pulse pressure, and the number of leads for ST-segment elevation. The nomogram involving these five risk factors showed full calibration and discrimination in the training group, with an AUC of 0.71 (95% CI: 0.66-0.77). It was confirmed in the validation group, and the entire cohort and the AUC were 0.64 (95% CI: 0.56-0.73) and 0.69 (95% CI: 0.65-0.74), respectively. Whether in the training group or the verification group, the calibration curve for the probability of no-reflow phenomenon all showed considerable consistency between prediction by nomogram and actual observation. The decision curve revealed a specific role in our nomogram in clinical practice. CONCLUSIONS: We set up a nomogram that showed absolute accuracy for the prediction of the risk of no-reflow after primary PCI in elderly STEMI patients.

Transcriptional network modulated by the prognostic signature transcription factors and their long noncoding RNA partners in primary prostate cancer.

BACKGROUND: Transcriptional regulators are seminal players in the onset and progression of prostate cancer. However, clarification of their underlying regulatory circuits and mechanisms demands considerable effort. METHODS: Integrated analyses were performed on genomic, transcriptomic, and clinicopathological profiles of primary prostate cancer and transcription factor-binding profiles, which included estimating transcription factor activity, identifying transcription factors of prognostic values, and discovering cis- and trans-regulations by long noncoding RNAs. Interactions between transcription factors and long noncoding RNAs were validated by RNA immunoprecipitation quantitative PCR. RNA interference assays were performed to explore roles of the selected transcription regulators. FINDINGS: Sixteen transcription factors, namely, ETS1, ARID4B, KLF12, GMEB1, HBP1, MXI1, MYC, MAX, PGR, BCL11A, AR, KLF4, SRF, HIF1A, EHF, and ATOH1, were jointly identified as a prognostic signature. Candidate long noncoding RNAs interplaying with the prognostic signature constituent transcription factors were further discovered. Their interactions were randomly checked, and many of them were experimentally proved. Transcription regulation by MYC and its long noncoding RNA partner AL590617.2 was further validated on their candidate targets. Moreover, the regulatory network governed by the transcription factors and their interacting long noncoding RNA partners is illustrated and stored in our LNCTRN database (https://navy.shinyapps.io/lnctrn). INTERPRETATION: The prognostic signature constituent transcription factors and their interacting long noncoding RNAs may represent promising biomarkers and/or therapeutic targets for prostate cancer. Furthermore, the computational framework proposed in the present study can be utilized to explore critical transcriptional regulators in other types of cancer. FUNDING: This work was supported by National Natural Science Foundation of China and Fudan University.

Impact of updated pediatric hypertension criteria on prevalence estimates of hypertension among Chinese children.

This study aimed to evaluate the impact of updated pediatric hypertension (HTN) criteria (the 2017 AAP Guidelines) on prevalence estimates of HTN and prehypertension among Chinese children compared to the 2004 Fourth Report. A total of 2093 children aged 7-15 years from five schools in Tianjin, China were selected using a multistage random cluster sampling method. The prevalence of HTN per the 2017 AAP Guidelines (10.1%) was significantly higher than that per the Fourth Report (6.6%), whereas the prevalence of prehypertension per the 2017 AAP Guidelines (6.3%) was significantly lower than that per the Fourth Report (8.8%). From the 2004 Fourth Report to the 2017 AAP Guidelines, a total of 117 (5.6%) children were reclassified to have higher blood pressure. The two criteria had better consistency in the diagnosis of systolic abnormalities than in the diagnosis of diastolic abnormalities. The updated definitions for pediatric HTN have a substantive impact on the prevalence estimation among Chinese children, especially among boys, overweight children, and older children.

Systematic Investigation of mRNA N 6-Methyladenosine Machinery in Primary Prostate Cancer.

BACKGROUND: Appreciable findings have pointed out pivotal roles of N 6-methyladenosine (m6A) machinery in cancer onset and progression. However, limited efforts have been directed towards relevant research in the prostate cancer area. METHODS: A PubMed search was conducted to acquire components of the mRNA m6A machinery. Multiomics integration was performed to systematically investigate the mRNA m6A machinery in primary prostate cancer. Furthermore, RNA interference assays of two prognostic m6A readers EIF3D and HNRNPA2B1 were conducted to explore m6A dependence of their functions in prostate cancer cell proliferation and migration. RESULTS: A total of 41 mRNA m6A regulators have been identified to date. A small degree of copy number aberrations and an extremely low frequency of somatic mutations were observed in the regulators across prostate tumors. Enrichment of CpG sites and extensive changes of DNA methylation in the m6A machinery were also found. Impact of copy number variation on m6A regulator expression was stronger than that of DNA methylation disturbance. Furthermore, our study identified a set of m6A regulators related to clinical features and/or survival which were largely m6A-binding proteins. The translation initiation factor subunit EIF3D and the splicing factor HNRNPA2B1 can be independent prognostic factors which may contribute to retardation and promotion of cancer progression, respectively, through affecting cancer-related processes such as cell cycle. Moreover, in vitro assays demonstrated that m6A impacted the EIF3D and HNRNPA2B1 roles in proliferation and migration of prostate cancer cells. CONCLUSIONS: Our report systematically described molecular features of the mRNA m6A machinery and their potential roles in primary prostate cancer. Knowledge gained from this work may pave the way for further studies on the m6A system in prostate cancer.

Comprehensive Characterization of Androgen-Responsive lncRNAs Mediated Regulatory Network in Hormone-Related Cancers.

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.