The interaction of macrophages and CD8 T cells in bronchoalveolar lavage fluid is associated with latent tuberculosis infection.

Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune responses. However, the immune mechanisms that govern the progression from LTBI to TB remain poorly defined in humans. Here, we profiled the lung immune cell populations within the bronchoalveolar lavage fluid (BALF) from patients with LTBI or TB using single-cell RNA sequencing (scRNA-seq). We found that Mtb infection substantially changed the immune cell compartments in the BALF, especially for the three subsets of macrophages, monocyte macrophage (MM)-CCL23, MM-FCN1, and MM-SPP1, which were found to be associated with the disease status of TB infection. Notably, MM-CCL23 cells derived from monocytes after stimulation with Mtb were characterized by high levels of chemokine (CCL23 and CXCL5) production and might serve as a marker for Mtb infection. The MM-CCL23 population mainly recruited CD8-CCR6 T cells through CCL20/CCR6, which was a prominent feature associated with protection immunity in LTBI. This study improves our understanding of the lung immune landscape during Mtb infection, which may inform future vaccine design for protective immunity.

Breakthrough infection evokes the nasopharyngeal innate immune responses established by SARS-CoV-2-inactivated vaccine.

Nasopharyngeal immune responses are vital for defense against SARS-CoV-2 infection. Although vaccination via muscle immunization has shown a high efficacy in reducing severity and death in COVID-19 infection, breakthrough infection frequently happens because of mutant variants and incompletely established mucosal immunity, especially in the upper respiratory tract. Here, we performed a single-cell RNA and T-cell receptor repertoire sequencing and delineated a high-resolution transcriptome landscape of nasopharyngeal mucosal immune and epithelial cells in vaccinated persons with breakthrough infection and non-vaccinated persons with natural infection as control. The epithelial cells showed anti-virus gene expression diversity and potentially recruited innate immune cells into the nasopharyngeal mucous of vaccinated patients. Upon infection, they released significant pro-inflammatory cytokines and chemokines by macrophages and monocytes and expressed antigen-presenting relevant genes by dendritic cells. Such immune responses of nasopharyngeal innate immune cells would facilitate the strengthened expression of cytotoxic genes in virus-specific T-cell or B-cell differentiation into antibody-secreting cells at the early stage of breakthrough infection through cell interaction between innate and adaptive immune cells. Notably, these alterations of nasopharyngeal immune cells in breakthrough infection depended on the activated Nuclear factor-κB (NF-κB) and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) signaling rather than type I interferon responses due to the general reduction in interferon-stimulated gene expression. Our findings suggest that vaccination potentially strengthens innate immune barriers and virus-specific memory immune cell responses, which could be quickly activated to defend against variant breakthrough infection and maintain nasopharyngeal epithelial cell integrity. Thus, this study highlights the necessity of a boost via nasal mucous after intramuscular immunization.

The role of redox-mediated lysosomal dysfunction and therapeutic strategies.

Redox homeostasis refers to the dynamic equilibrium between oxidant and reducing agent in the body which plays a crucial role in maintaining normal physiological activities of the body. The imbalance of redox homeostasis can lead to the development of various human diseases. Lysosomes regulate the degradation of cellular proteins and play an important role in influencing cell function and fate, and lysosomal dysfunction is closely associated with the development of various diseases. In addition, several studies have shown that redox homeostasis plays a direct or indirect role in regulating lysosomes. Therefore, this paper systematically reviews the role and mechanisms of redox homeostasis in the regulation of lysosomal function. Therapeutic strategies based on the regulation of redox exerted to disrupt or restore lysosomal function are further discussed. Uncovering the role of redox in the regulation of lysosomes helps to point new directions for the treatment of many human diseases.

Photoactivated Hydrogen Sulfide Donor with a Near-Infrared Fluorescence Report System for Accelerated Chronic Wound Healing.

Delayed wound healing is one of the major diabetes complications that occur in 25% of diabetic patients. Specific wound management and combination treatment are required to repair the wound, which still remains a challenge with few effective therapies available currently. In this work, a new H2S donor PRO-F, which is characterized by the capability to promote wound healing in diabetes, was designed. PRO-F can be activated by light without consuming endogenous substances and the accompanying fluorescent signal makes the real-time tracking of released H2S possible. PRO-F is able to deliver H2S in an intracellular environment with moderate release efficiency (50%), which presents cytoprotective effects against excessive reactive oxygen species (ROS) induced damage. Furthermore, the potential of PRO-F to enhance chronic wound healing was validated by employing diabetic models. This work provides new insights into the therapeutic role of H2S donors in complex wound conditions, which should advance the pathophysiological research associated with H2S.

An EPFL peptide signaling pathway promotes stamen elongation via enhancing filament cell proliferation to ensure successful self-pollination in Arabidopsis thaliana.

Proper stamen filament elongation is essential for plant self-pollination and reproduction. Several phytohormones such as jasmonate and gibberellin play important roles in controlling filament elongation, but other endogenous signals involved in this developmental process remain unknown. We report here that three EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family peptides, EPFL4, EPFL5 and EPFL6, act redundantly to promote stamen filament elongation via enhancing filament cell proliferation in Arabidopsis thaliana. Knockout of EPFL4-6 genes led to shortened filaments due to defective filament cell proliferation, resulting in pollination failure and male sterility. Further genetic and biochemical analyses indicated that the ERECTA family and the SOMATIC EMBRYOGENESIS RECEPTOR KINASE (SERK) family RLKs form receptor complexes to perceive EPFL4-6 peptides and promote filament cell proliferation. Moreover, based on both loss- and gain-of-function genetic analyses, the mitogen-activated protein kinase cascade MKK4/MKK5-MPK6 was shown to function downstream of EPFL4-6 to positively regulate cell proliferation in stamen filaments. Together, this study reveals that an EPFL peptide signaling pathway composed of the EPFL4-6 peptide ligands, the ERECTA-SERK receptor complexes and the downstream MKK4/MKK5-MPK6 cascade promotes stamen filament elongation via enhancing filament cell proliferation to ensure successful self-pollination and normal fertility in Arabidopsis.

NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-ß/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer.

Pancreatic cancer (PaCa) is one of the most fatal malignancies of the digestive system, and most patients are diagnosed at advanced stages due to the lack of specific and effective tumor-related biomarkers for the early detection of PaCa. miR-492 has been found to be upregulated in PaCa tumor tissue and may serve as a potential therapeutic target. However, the molecular mechanisms by which miR-492 promotes PaCa tumor growth and progression are unclear. In this study, we first found that miR-492 in enhancer loci activated neighboring genes (NR2C1/NDUFA12/TMCC3) and promoted PaCa cell proliferation, migration, and invasion in vitro. We also observed that miR-492-activating genes significantly enriched the TGF-ß/Smad3 signaling pathway in PaCa to promote epithelial-mesenchymal transition (EMT) during tumorigenesis and development. Using CRISPR-Cas9 and ChIP assays, we further observed that miR-492 acted as an enhancer trigger, and that antagomiR-492 repressed PaCa tumorigenesis in vivo, decreased the expression levels of serum TGF-ß, and suppressed the EMT process by downregulating the expression of NR2C1. Our results demonstrate that miR-492, as an enhancer trigger, facilitates PaCa progression via the NR2C1-TGF-ß/Smad3 pathway.

5-mRNA-based prognostic signature of survival in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common non-small-cell lung cancer, with a high incidence and a poor prognosis. AIM: To construct effective predictive models to evaluate the prognosis of LUAD patients. METHODS: In this study, we thoroughly mined LUAD genomic data from the Gene Expression Omnibus (GEO) (GSE43458, GSE32863, and GSE27262) and the Cancer Genome Atlas (TCGA) datasets, including 698 LUAD and 172 healthy (or adjacent normal) lung tissue samples. Univariate regression and LASSO regression analyses were used to screen differentially expressed genes (DEGs) related to patient prognosis, and multivariate Cox regression analysis was applied to establish the risk score equation and construct the survival prognosis model. Receiver operating characteristic curve and Kaplan-Meier survival analyses with clinically independent prognostic parameters were performed to verify the predictive power of the model and further establish a prognostic nomogram. RESULTS: A total of 380 DEGs were identified in LUAD tissues through GEO and TCGA datasets, and 5 DEGs (TCN1, CENPF, MAOB, CRTAC1 and PLEK2) were screened out by multivariate Cox regression analysis, indicating that the prognostic risk model could be used as an independent prognostic factor (Hazard ratio = 1.520, P < 0.001). Internal and external validation of the model confirmed that the prediction model had good sensitivity and specificity (Area under the curve = 0.754, 0.737). Combining genetic models and clinical prognostic factors, nomograms can also predict overall survival more effectively. CONCLUSION: A 5-mRNA-based model was constructed to predict the prognosis of lung adenocarcinoma, which may provide clinicians with reliable prognostic assessment tools and help clinical treatment decisions.

Identification of prognostic immune-related lncRNAs in pancreatic cancer.

Long noncoding RNAs (lncRNAs) play a critical role in the immune regulation and tumor microenvironment of pancreatic cancer (PaCa). To construct a novel immune-related prognostic risk model for PaCa and evaluate the prognostic prediction of lncRNAs, essential immune-related lncRNAs (IRlncRNAs) were identified by Pearson correlation analysis of differentially expressed immune-related genes (IRGs) and IRlncRNAs in PaCa from The Cancer Genome Atlas (TCGA) and GTEx databases. Least absolute shrinkage and selection operator (LASSO) regression was also applied to construct a prognostic risk model of IRlncRNAs, and gene set enrichment analysis (GSEA) was further applied for functional annotation for these IRlncRNAs. A total of 148 IRlncRNAs were identified in PaCa to construct a prognostic risk model. Among them, lncRNA LINC02325, FNDC1-AS1, and ZEB2-AS1 were significantly upregulated in 69 pairs of PaCa tissues by qRT-PCR. ROC analyses showed that LINC02325 (AUC = 0.80), FNDC1-AS1 (AUC = 0.76), and ZEB2-AS1 (AUC = 0.75) had a good predictive effect on 5-year survival prognosis. We demonstrated that high expression levels of ZEB2-AS1 and LINC02325 were not only positively associated with tumor size and CA199, but elevated levels of ZEB2-AS1 and FNDC1-AS1 were also positively correlated with tumor stage. GSEA further revealed that immune-related pathways were mainly enriched in the high-risk groups. Several immune-related algorithms demonstrated that four IRlncRNAs were related to immune infiltration, immune checkpoints, and immune-related functions. Thus, the prognostic risk model based on IRlncRNAs in Paca indicates that the four IRlncRNA signatures may serve as predictors of survival and potential predictive biomarkers of the pancreatic tumor immune response.

Discovery and Optimization of Quinoline Analogues as Novel Potent Antivirals against Enterovirus D68.

Enterovirus D68 (EV-D68) is a nonpolio enterovirus that is mainly transmitted through respiratory routes and poses a potential threat for large-scale spread. EV-D68 infections mostly cause moderate to severe respiratory diseases in children and potentially induce neurological diseases. However, there are no specific antiviral drugs or vaccines against EV-D68. Herein, through virtual screening and rational design, a series of novel quinoline analogues as anti-EV-D68 agents targeting VP1 were identified. Particularly, 19 exhibited potent antiviral activity with an EC50 value ranging from 0.05 to 0.10 µM against various EV-D68 strains and showed inhibition of viral replication verified by Western blot, immunofluorescence, and plaque formation assay. Mechanistic studies indicated that the anti-EV-D68 agents work mainly by interacting with VP1. The acceptable bioavailability of 23.9% in rats and significant metabolic stability in human liver microsome (Clint = 10.8 mL/min/kg, t1/2 = 148 min) indicated that compound 19 with a novel scaffold was worth further investigation.

Angiotensin-Converting Enzyme 2 SNPs as Common Genetic Loci and Optimal Early Identification Genetic Markers for COVID-19.

Background: Angiotensin-converting enzyme 2 (ACE2) is implicated as a host cell receptor that causes infection in the pathogenesis of coronavirus disease 2019 (COVID-19), and its genetic polymorphisms in the ACE2 gene may promote cardiovascular disease and systemic inflammatory injury in COVID-19 patients. Hence, the genetic background may potentially explain the broad interindividual variation in disease susceptibility and/or severity. Methods: Genetic susceptibility to COVID-19 was analyzed by examining single-nucleotide polymorphisms (SNPs) of ACE2 in 246 patients with COVID-19 and 210 normal controls using the TaqMan genotyping assay. Results: We demonstrated that the ACE2 SNPs rs4646142, rs6632677, and rs2074192 were associated with COVID-19 (for all, p < 0.05), and the differences in the ACE2 SNPs rs4646142 and rs6632677 were correlated with COVID-19-related systemic inflammatory injury and cardiovascular risk. Specifically, rs4646142 was associated with high-sensitivity C-reactive protein (hs-CRP), prealbumin (PAB), apolipoprotein A (APOA), high-density lipoprotein (HDL), and acid glycoprotein (AGP) levels. Rs6632677 was also associated with elevated CRP, acid glycoprotein (AGP), and haptoglobin (HPT). Conclusions: Our results suggest that the ACE2 SNPs rs4646142 and rs6632677 may be common genetic loci and optimal early identification genetic markers for COVID-19 with cardiovascular risk.

Comprehensive RNA-seq reveals molecular changes in kidney malignancy among people living with HIV.

To heighten the awareness of kidney malignancy in patients with HIV infection to facilitate the early diagnosis of kidney cancer, the differentially expressed mRNAs were analyzed in this malignant tumor using RNA sequencing. We identified 2,962 protein-coding transcripts in HIV-associated kidney cancer. KISS1R, CAIX, and NPTX2 mRNA expression levels were specifically increased in HIV-associated kidney cancer while UMOD and TMEM213 mRNA were decreased in most cases based on real-time PCR analyses. These findings were similar to those noted for the general population with renal cell carcinoma. Immunohistochemical staining analysis also showed that a total of 18 malignant kidney cases among the people living with HIV (PLWH) exhibited positive staining for KISS1R and CAIX. Pathway analysis of the differentially expressed mRNAs in HIV-associated kidney cancer revealed that several key pathways were involved, including vascular endothelial growth factor-activated receptor activity, IgG binding, and lipopolysaccharide receptor activity. Altogether, our findings reveal the identified molecular changes in kidney malignancy, which may offer a helpful explanation for cancer progression and open up new therapeutic avenues that may decrease mortality after a cancer diagnosis among PLWH.

LncRNAs as epigenetic regulators of epithelial to mesenchymal transition in pancreatic cancer.

Pancreatic cancer is the leading cause of cancer-related mortality because of tumor metastasis. Activation of the epithelial-to-mesenchymal transition (EMT) pathway has been confirmed to be an important driver of pancreatic cancer progression from initiation to metastasis. Long noncoding RNAs (lncRNAs) have been reported to exert essential physiological functions in pancreatic cancer progression by regulating the EMT program. In this review, we have summarized the role of EMT-related lncRNAs in human pancreatic cancer and the potential molecular mechanisms by which lncRNAs can be vital epigenetic regulators of epithelial to mesenchymal transition. Specifically, EMT-activating transcription factors (EMT-TFs) regulate EMT via TGF-ß/Smad, Wnt/ß-catenin, and JAK/STAT pathways. In addition, the interaction between lncRNAs and HIF-1α and m6A RNA methylation also have an impact on tumor metastasis and EMT in pancreatic cancer. This review will provide insights into lncRNAs as promising biomarkers for tumor metastasis and potential therapeutic strategies for pancreatic cancer.

Preliminary Efficacy and Safety of Camrelizumab in Combination With XELOX Plus Bevacizumab or Regorafenib in Patients With Metastatic Colorectal Cancer: A Retrospective Study.

BACKGROUND: For a majority of patients with metastatic colorectal cancer (mCRC) with MS stable (MSS) or mismatch repair proficient (pMMR), the role of immunotherapy is undetermined. This study investigated the efficacy and safety of camrelizumab when added to XELOX chemotherapy plus bevacizumab or regorafenib as first-line therapy for mCRC. MATERIALS AND METHODS: Medical records of mCRC patients who received camrelizumab and XELOX plus bevacizumab or regorafenib at the First Hospital of Quanzhou Affiliated to Fujian Medical University between June 1, 2019, and April 30, 2021, were retrospectively collected. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and side effects of the drug were recorded and reviewed. RESULTS: Twenty-five eligible patients received combination therapy, including bevacizumab in 19 patients and regorafenib in 6. Twenty-one patients had pMMR/MSS and one MSI-H. Of the 25 patients who could be evaluated for efficacy, 18 (72%) achieved PR, 6 (24%) achieved SD, and 1 (4%) achieved PD. The ORR and DCR were 72% (18/25) and 96% (24/25), respectively. The median progression-free survival (PFS) was 11.2 months (95% CI 8.9-13.9), and OS had not yet been reached. The combination regimen of regorafenib in six (24%) patients was unassociated with treatment outcomes. Most AEs were either grade 1 or 2, and treatment-related grade 3 toxicities were observed in 8/25 (32%) patients. CONCLUSION: Camrelizumab combined with XELOX plus bevacizumab or regorafenib was feasible, producing high rates of responses as first-line therapy in unselected Chinese patients with MSS mCRC. The toxicities were generally tolerable and manageable. Prospective randomized trials with large sample sizes are needed to evaluate these findings.

Monitoring Coronavirus Disease 2019: A Review of Available Diagnostic Tools.

Coronavirus disease 2019 (COVID-19) pneumonia is caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has rapidly become a global public health concern. As the new type of betacoronavirus, SARS-CoV-2 can spread across species and between populations and has a greater risk of transmission than other coronaviruses. To control the spread of SARS-CoV-2, it is vital to have a rapid and effective means of diagnosing asymptomatic SARS-CoV-2-positive individuals and patients with COVID-19, an early isolation protocol for infected individuals, and effective treatments for patients with COVID-19 pneumonia. In this review, we will summarize the novel diagnostic tools that are currently available for coronavirus, including imaging examinations and laboratory medicine by next-generation sequencing (NGS), real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) analysis, immunoassay for COVID-19, cytokine and T cell immunoassays, biochemistry and microbiology laboratory parameters in the blood of the patients with COVID-19, and a field-effect transistor-based biosensor of COVID-19. Specifically, we will discuss the effective detection rate and assay time for the rRT-PCR analysis of SARS-CoV-2 and the sensitivity and specificity of different antibody detection methods, such as colloidal gold and ELISA using specimen sources obtained from the respiratory tract, peripheral serum or plasma, and other bodily fluids. Such diagnostics will help scientists and clinicians develop appropriate strategies to combat COVID-19.

Metabolic defects in splenic B cell compartments from patients with liver cirrhosis.

Liver cirrhosis is associated with defective vaccine responses and increased infections. Dysregulated B cell compartments in cirrhotic patients have been noticed but not well characterized, especially in the spleen. Here, we comprehensively investigated B cell perturbations from the spleens and peripheral blood of cirrhotic patients. We found that liver cirrhosis significantly depleted both switched and nonswitched splenic memory B cells, which was further confirmed histologically. Bulk RNA-seq revealed significant metabolic defects as the potential mechanism for the impaired splenic B cell functions. Functionally, the splenic memory B cells from cirrhotic patients showed strong metabolic defects and reduced proliferation compared with those from healthy controls. Thus, liver cirrhosis extensively disturbs the splenic and peripheral B cell compartments, which may contribute to defective humoral immunity during liver cirrhosis.

Design, synthesis and biological activities of piperidine-spirooxadiazole derivatives as α7 nicotinic receptor antagonists.

α: 7 nicotinic acetylcholine receptors (nAChRs) expressed in the nervous and immune systems have been suggested to play important roles in the control of inflammation. However, the lack of antagonist tools specifically inhibiting α7 nAChR impedes the validation of the channel as therapeutic target. To discover a selective α7 antagonist, we started a pharmacophore-based virtual screening and identified a piperidine-spirooxadiazole derivative T761-0184 that acts as a α7 antagonist. A series of novel piperidine-spirooxadiazole derivatives were subsequently synthesized and evaluated using two-electrode voltage clamp (TEVC) assay in Xenopus oocytes. Lead compounds from two series inhibited α7 with their IC50 values ranging from 3.3 µM to 13.7 µM. Compound B10 exhibited α7 selectivity over other α4ß2 and α3ß4 nAChR subtypes. The analysis of structure-activity relationship (SAR) provides valuable insights for further development of selective α7 nAChR antagonists.

Mathematical models for devising the optimal SARS-CoV-2 strategy for eradication in China, South Korea, and Italy.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spreads rapidly and has attracted worldwide attention. METHODS: To improve the forecast accuracy and investigate the spread of SARS-CoV-2, we constructed four mathematical models to numerically estimate the spread of SARS-CoV-2 and the efficacy of eradication strategies. RESULTS: Using the Susceptible-Exposed-Infected-Removed (SEIR) model, and including measures such as city closures and extended leave policies implemented by the Chinese government that effectively reduced the ß value, we estimated that the ß value and basic transmission number, R0, of SARS-CoV-2 was 0.476/6.66 in Wuhan, 0.359/5.03 in Korea, and 0.400/5.60 in Italy. Considering medicine and vaccines, an advanced model demonstrated that the emergence of vaccines would greatly slow the spread of the virus. Our model predicted that 100,000 people would become infected assuming that the isolation rate α in Wuhan was 0.30. If quarantine measures were taken from March 10, 2020, and the quarantine rate of α was also 0.3, then the final number of infected people was predicted to be 11,426 in South Korea and 147,142 in Italy. CONCLUSIONS: Our mathematical models indicate that SARS-CoV-2 eradication depends on systematic planning, effective hospital isolation, and SARS-CoV-2 vaccination, and some measures including city closures and leave policies should be implemented to ensure SARS-CoV-2 eradication.

Single-cell RNA sequencing reveals the heterogeneity of liver-resident immune cells in human.

The liver plays a critical role in both immune defense and tolerance in the body. The liver-resident immune cells (LrICs) determine the immune properties, but the unique composition and heterogeneity of these cells are incompletely understood. Here, we dissect the diversity of LrICs by a comprehensive transcriptomic profiling using the unbiased single-cell RNA-sequencing (scRNA-seq). A total of 70, 706 of CD45+ immune cells from the paired liver perfusion, spleen and peripheral blood as references were profiled. We identified more than 30 discrete cell populations comprising 13 of T and NK cell, 7 of B cell, 4 of plasma cell, and 8 of myeloid cell subsets in human liver and donor-paired spleen and blood, and characterized their tissue distribution, gene expression and functional modules. Especially, four of CXCR6+ T and NK cell subsets were found to be present preferentially in the liver, where they manifested heterogeneity, distinct function and prominent homeostatic proliferation. We propose a universal category system of T and NK cells based on distinct chemokine receptors, confirmed subsequently by phenotype, transcriptional factors and functionality. We also identified adaptive changes by the spleen and liver-derived monocyte and macrophage populations. Finally, we give a global glimpse on B cell and plasma cell subsets in human spleen and liver. We, therefore, reveal the heterogeneity and functional diversity of LrICs in human. This study presents comprehensively the landscape of LrICs and will enable further study on their roles in various human diseases.

Identification of Specific Long Non-Coding Ribonucleic Acid Signatures and Regulatory Networks in Prostate Cancer in Fine-Needle Aspiration Biopsies.

Prostate cancer (PCa) is one of the most common tumors in men and can be lethal, especially if left untreated. A substantial majority of PCa patients not only are diagnosed based on fine needle aspiration (FNA) biopsies, but their treatment choices are also largely driven by the pathological findings obtained with these FNA specimens. It is widely believed that lncRNAs have strong biological significance, but their specific functions and regulatory networks have not been elucidated. LncRNAs may serve as key players and regulators of PCa carcinogenesis and could be novel biomarkers of this cancer. To identify potential markers for early detection of PCa, in this study, we employed a competing endogenous RNA (ceRNA) microarray to identify differentially expressed lncRNAs (DelncRNAs) in PCa tissue and quantitative real-time PCR (qRT-PCR) analysis to validate these DelncRNAs in FNA biopsies. We demonstrated that a total of 451 lncRNAs were differentially expressed in four pairs of PCa/adjacent tissues, and upregulation of the lncRNAs RP11-33A14.1, RP11-423H2.3, and LAMTOR5-AS1 was confirmed in FNA biopsies of PCa by qRT-PCR and was consistent with the ceRNA array data. The association between the expression of the lncRNA LAMTOR5-AS1 and aggressive cancer was also investigated. Regulatory network analysis of DelncRNAs showed that the lncRNAs RP11-33A14.1 and RP11-423H2.3 targeted miR-7, miR-24-3p, and miR-30 and interacted with the RNA binding protein FUS. Knockdown of these DelncRNAs in PCa cells also demonstrated the effects of RP11-423H2.3 on miR-7/miR-24/miR-30 or LAMTOR5-AS1 on miR-942-5p/miR-542-3p via direct interaction. The results of these studies indicate that these three specific lncRNA signatures and regulatory networks might serve as risk prediction and diagnostic biomarkers for prostate cancer, even in biopsies obtained by FNA.