Circular RNAs in laryngeal cancer.

Laryngeal cancer remains a significant global health concern, with poor prognosis for advanced-stage disease highlighting the need for novel diagnostic, prognostic, and therapeutic approaches. Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, have emerged as important regulators of gene expression and cellular processes in various cancers, including laryngeal cancer. This review summarizes the current understanding of circRNAs in laryngeal cancer, covering their biogenesis, regulatory mechanisms, and potential clinical applications. We explore the diverse functions of circRNAs, including their roles as miRNA sponges, protein interactors, and direct mRNA regulators, and their influence on key cellular processes such as proliferation, invasion, and metastasis. The review highlights promising circRNAs as diagnostic and prognostic biomarkers, as well as potential therapeutic targets. We also outline current strategies for circRNA modulation, including suppression techniques like RNA interference and CRISPR/Cas systems, and overexpression methods using vectors and synthetic circRNAs.

Association of long noncoding RNA GAS5 gene polymorphism with progression of diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, whose complex etiology involves a genetic component. Growth arrest-specific 5 (GAS5), a long noncoding RNA (lncRNA) gene, has been recently shown to regulate renal fibrosis. Here, we aimed to explore the potential role of GAS5 gene polymorphisms in the predisposition to DKD. One single-nucleotide (rs55829688) and one insertion/deletion polymorphism (rs145204276) of GAS5 gene were surveyed in 778 DKD cases and 788 DKD-free diabetic controls. We demonstrated that diabetic subjects who are heterozygous at rs55829688 (TC; AOR, 1.737; 95% CI, 1.028-2.937; p=0.039) are more susceptible to advanced DKD but not early-staged DKD, as compared to diabetic subjects who are homozygous for the major allele of rs55829688 (TT). Carriers of at least one minor allele (C) of rs55829688 (TC and CC; AOR, 1.317; 95% CI, 1.023-1.696; p=0.033) more frequently suffer from advanced DKD than do those homozygotes for the major allele (TT). Furthermore, in comparison to those who do not carry the minor allele of rs55829688 (TT), advanced DKD patients possessing at least one minor allele of rs55829688 (TC and CC) exhibited a lower glomerular filtration rate, revealing an impact of rs55829688 on renal co-morbidities of diabetes. In conclusion, our data indicate an association of GAS5 gene polymorphisms with the progression of DKD.

Circular RNAs as a novel molecular mechanism in diagnosis, prognosis, therapeutic target, and inhibiting chemoresistance in breast cancer.

Breast cancer (BC) is the most common cancer among women, characterized by significant heterogeneity. Diagnosis of the disease in the early stages and appropriate treatment plays a crucial role for these patients. Despite the available treatments, many patients due to drug resistance do not receive proper treatments. Recently, circular RNAs (circRNAs), a type of non-coding RNAs (ncRNAs), have been discovered to be involved in the progression and resistance to drugs in BC. CircRNAs can promote or inhibit malignant cells by their function. Numerous circRNAs have been discovered to be involved in the proliferation, invasion, and migration of tumor cells, as well as the progression, pathogenesis, tumor metastasis, and drug resistance of BC. Circular RNAs can also serve as a biomarker for diagnosing, predicting prognosis, and targeting therapy. In this review, we present an outline of the variations in circRNAs expression in various BCs, the functional pathways, their impact on the condition, and their uses in clinical applications.

Epigenetic-modifying agents: the potential game changers in the treatment of hematologic malignancies.

Hematologic malignancies are lethal diseases arising from accumulated leukemic cells with substantial genetic or epigenetic defects in their natural development. Epigenetic modifications, including DNA methylation and histone modifications, are critical in hematologic malignancy formation, propagation, and treatment response. Both mutations and aberrant recruitment of epigenetic modifiers are reported in different hematologic malignancies, which regarding the reversible nature of epigenetic regulations, make them a potential target for cancer treatment. Here, we have first outlined a comprehensive overview of current knowledge related to epigenetic regulation's impact on the development and prognosis of hematologic malignancies. Furthermore, we have presented an updated overview regarding the current status of epigenetic-based drugs in hematologic malignancies treatment. And finally, discuss current challenges and ongoing clinical trials based on the manipulation of epigenetic modifies in hematologic malignancies.

Overexpression of Long Non-coding RNAs MCM3AP-AS1 and LINC00092 Predict Poor Prognosis in Patients with Gastric Adenocarcinoma.

Background: LINC00092 and MCM3AP-AS1 long non-coding RNAs (LncRNAs) play significant roles in the development and pathogenesis of many cancers. However, their expression levels and prognostic values were not evaluated in human gastric adenocarcinoma (GAC). Therefore, the present study aimed to investigate the clinico-pathological correlations of LINC00092 and MCM3AP-AS1, LncRNAs expression in GAC, and evaluate their prognostic values. Materials and Methods: The expression of LINC00092 and MCM3AP-AS1 was detected in 89 GAC tissues by quantitative real-time reverse-transcription PCR (qRT-PCR). Results: Our results showed that LINC00092 and MCM3AP-AS1 are overexpressed in GAC patients and positively correlated with GAC invasion and vascular, peritoneal, and lymph node metastasis (P < 0.05). Furthermore, the results indicated that MCM3AP-AS1 (P = 0.0225) and LINC00092 (P < 0.001) have positive correlations with GAC patients' overall survival. Conclusion: Altogether, the present results indicated that LINC00092 and MCM3AP-AS1 overexpression is associated with clinico-pathological characteristic of GAC patients. In addition, both of these LncRNAs may have prognostic value for estimation of patients' overall survival.

Prognostic significance of non-coding RNAs related to the tumorigenic epithelial-mesenchymal transition (EMT) process among ovarian cancer patients: A systematic review and meta-analysis.

Introduction: Ovarian cancer is the seventh most prevalent cancer among women. It has high mortality and morbidity and imposes a great burden on healthcare systems worldwide. Unraveling the mechanisms behind the Epithelial-Mesenchymal Transition and finding a panel for predicting the prognosis of the disease may help find the appropriate treatment approaches for the management of the disease. The overarching aim of this systematic review was to define a panel of different types of EMT-associated non-coding RNAs (ncRNAs) with significant prognostic value in all types of ovarian cancers. Methods: We searched PubMed, Web of Science, Scopus, and Embase till Jun 2024 to retrieve relevant papers. Two independent reviewers screened papers, and discrepancies were resolved by consensus. Publications related to the dysregulation of different types of ncRNAs, including microRNAs, lncRNAs, and circRNAs, only in patients with ovarian cancer were included. The participation of ncRNAs in epithelial-mesenchymal transformation should be assessed via methods evaluating different EMT-related proteins. To assess the quality and risk of bias for the included case-control and cohort studies, refined Newcastle-Ottawa Scale (NOS) and Quadas-2 were recruited. A bivariate meta-analysis was performed to analyze extracted data. Results: A total of 37 studies with overall 42 non-coding RNAs (15 microRNA, 24 long non-coding RNAs, and 3 circular RNAs) were entered into the analysis. Overall diagnostic odds ratio for ncRNAs in lymph node metastasis, distant metastasis, TNM stage, and clinical stage were 4.19, 3.80, 6.52, and 3.97, respectively. Also, a hazard ratio of 1.39 (P = 0.32) for overall survival was observed. Bioinformatic analyses on the Pan-cancer database demonstrated a significant correlation between low expression of miRNA and high expression of lncRNAs with poor prognosis of ovarian cancer. Conclusion: Based on the results, the defined panel of ncRNAs can properly predict prognostic factors related to EMT in ovarian cancer without involving potentially invasive methods.

DNA damage response-related ncRNAs as regulators of therapy resistance in cancer.

The DNA damage repair (DDR) pathway is a complex signaling cascade that can sense DNA damage and trigger cellular responses to DNA damage to maintain genome stability and integrity. A typical hallmark of cancer is genomic instability or nonintegrity, which is closely related to the accumulation of DNA damage within cancer cells. The treatment principles of radiotherapy and chemotherapy for cancer are based on their cytotoxic effects on DNA damage, which are accompanied by severe and unnecessary side effects on normal tissues, including dysregulation of the DDR and induced therapeutic tolerance. As a driving factor for oncogenes or tumor suppressor genes, noncoding RNA (ncRNA) have been shown to play an important role in cancer cell resistance to radiotherapy and chemotherapy. Recently, it has been found that ncRNA can regulate tumor treatment tolerance by altering the DDR induced by radiotherapy or chemotherapy in cancer cells, indicating that ncRNA are potential regulatory factors targeting the DDR to reverse tumor treatment tolerance. This review provides an overview of the basic information and functions of the DDR and ncRNAs in the tolerance or sensitivity of tumors to chemotherapy and radiation therapy. We focused on the impact of ncRNA (mainly microRNA [miRNA], long noncoding RNA [lncRNA], and circular RNA [circRNA]) on cancer treatment by regulating the DDR and the underlying molecular mechanisms of their effects. These findings provide a theoretical basis and new insights for tumor-targeted therapy and the development of novel drugs targeting the DDR or ncRNAs.

The role of lncRNA binding to RNA­binding proteins to regulate mRNA stability in cancer progression and drug resistance mechanisms (Review).

Cancer is a disease that poses a serious threat to human health, the occurrence and development of which involves complex molecular mechanisms. Long non­coding RNAs (lncRNAs) and RNA­binding proteins (RBPs) are important regulatory molecules within cells, which have garnered extensive attention in cancer research in recent years. The binding of lncRNAs and RBPs plays a crucial role in the post­transcriptional regulation of mRNA, affecting the synthesis of proteins related to cancer by regulating the stability of mRNA. This, in turn, regulates the malignant biological behaviors of tumor cells, such as proliferation and metastasis, and serves an important role in therapeutic resistance. The present study reviewed the role of lncRNA­RBP interactions in the regulation of mRNA stability in various malignant tumors, with a focus on the molecular mechanisms underlying this regulatory interaction. The aim of the present review was to gain a deeper understanding of these molecular mechanisms to provide new strategies and insights for the precise treatment of cancer.

Schizophrenia risk-associated SNPs affect expression of microRNA 137 host gene: a postmortem study.

Common variants in the MicroRNA 137 host gene MIR137HG and its adjacent gene DPYD have been associated with schizophrenia risk and the latest Psychiatric Genomics Consortium (PGC). Genome-Wide Association Study on schizophrenia has confirmed and extended these findings. To elucidate the association of schizophrenia risk-associated SNPs in this genomic region, we examined the expression of both mature and immature transcripts of the miR-137 host gene (MIR137HG) in the dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex (sgACC) of postmortem brain samples of donors with schizophrenia and psychiatrically-unaffected controls using qPCR and RNA-Seq approaches. No differential expression of miR-137, MIR137HG, or its transcripts was observed. Two schizophrenia risk-associated SNPs identified in the PGC study, rs11165917 (DLPFC: P = 2.0e-16; sgACC: P = 6.4e-10) and rs4274102 (DLPFC: P = 0.036; sgACC: P = 0.002), were associated with expression of the MIR137HG long non-coding RNA transcript MIR137HG-203 (ENST00000602672.2) in individuals of European ancestry. Carriers of the minor (risk) allele of rs11165917 had significantly lower expression of MIR137HG-203 compared with those carrying the major allele. However, we were unable to validate this result by short-read sequencing of RNA extracted from DLPFC or sgACC tissue. This finding suggests that immature transcripts of MIR137HG may contribute to genetic risk for schizophrenia.

Immunoactive signatures of circulating tRNA- and rRNA-derived RNAs in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the most prevalent lung disease, and macrophages play a central role in the inflammatory response in COPD. We here report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma from patients with COPD. While circulating sncRNAs are increasingly recognized for their regulatory roles and biomarker potential in various diseases, the conventional RNA sequencing (RNA-seq) method cannot fully capture these circulating sncRNAs due to their heterogeneous terminal structures. By pre-treating the plasma RNAs with T4 polynucleotide kinase, which converts all RNAs to those with RNA-seq susceptible ends (5'-phosphate and 3'-hydroxyl), we comprehensively sequenced a wide variety of non-microRNA sncRNAs, such as 5'-tRNA halves containing a 2',3'-cyclic phosphate. We discovered a remarkable accumulation of the 5'-half derived from tRNAValCAC in plasma from COPD patients, whereas the 5'-tRNAGlyGCC half is predominant in healthy donors. Further, the 5'-tRNAValCAC half activates human macrophages via Toll-like receptor 7 and induces cytokine production. Additionally, we identified circulating rRNA-derived fragments that were upregulated in COPD patients and demonstrated their ability to induce cytokine production in macrophages. Our findings provide evidence of circulating, immune-active sncRNAs in patients with COPD, suggesting that they serve as inflammatory mediators in the pathogenesis of COPD.

Exploration and validation of ceRNA regulatory networks in colorectal cancer based on associations whole transcriptome sequencing.

Colorectal cancer (CRC) is a wide-spread gastrointestinal cancer that is associated with augmented morbidity and mortality, and we do not yet have a deep understanding of its epidemiology and carcinogenicity. The transcriptome can reveal the complexity and heterogeneity of tumors and uncover new biomarkers or treatment options. In this study, we identified messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), round RNAs (circRNAs), and microRNAs (miRNAs) using whole-transcriptome sequencing and generated competing endogenous RNA (ceRNA) modulatory axes. We conducted whole transcriptome sequencing on 10 CRC and para-cancer (CRCP) samples and discovered 2465 differentially expressed (DE) mRNAs (DEmRNAs), 77 DE miRNAs (DEmiRNAs). 2852 DE lncRNAs (DElncRNAs) and 1477 DE circRNAs (DEcircRNAs). In addition, utilizing co-DE analysis, we generated the ceRNA axis. Subsequently, we employed the ceRNA axis to identify essential genes and corresponding associations with lncRNAs, circRNAs, and miRNAs in CRC. ceRNA regulatory network including mRNA-miRNA-lncRNA and mRNA-miRNA-circRNA. These modulatory axes potentially modulate the positive regulation of smooth muscle contraction, melanosome, plasma membrane, integral plasma membrane component and so on. Finally, the results of RNA sequencing (RNA-SEQ) were combined with the TCGA and GEO databases, and the DEGs strongly correlated with the TCGA-COAD overall survival (OS) as estimated by univariate cox and logarithmic rank analyses were cross-analyzed, and the co-upregulated DEGs were screened. Among the many DEs, KPNA2 was chosen for additional analysis. Using invitro experimentations, western blot, CCK8, EdU and other experiments were performed to verify the results. We found siRNA-based KPNA2 depletion reduces bladder cancer cells' viability, migratory, and proliferative activities, which showed that the DEmRNA profiles were comparable to the sequencing information, confirming that the sequencing data were very reliable. These evidences highlight the ceRNA regulatory mechanisms in CRC and will aid future research into the molecular mechanisms behind colorectal cancer prevention and treatment.

Identification of LINC02454-related key pathways and genes in papillary thyroid cancer by weighted gene coexpression network analysis (WGCNA).

BACKGROUND: Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. METHODS: Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. RESULTS: The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM - receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. CONCLUSIONS: Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC.

LncRNA HOXB-AS3 promotes proliferation, migration, and invasion of gallbladder cancer cells by activating the MEK/ERK pathway.

Background: LncRNA HOXB-AS3 are associated with tumor progression in several types of carcinomas, yet, its possibly biological role in gallbladder carcinoma(GBC) remains unclear. Therefore, this study aimed to investigate the biological function of HOXB-AS3 in GBC. Methods: To know the potential function of HOXB-AS3 in gallbladder carcinoma, real-time polymerase chain reaction was used to detected the expression of HOXB-AS3 in gallbladder carcinoma cells. The colony formation assay and cell counting kit-8 assay was performed to measured cell viability. Flow cytometry was to analyse cell apoptosis and cell cycle. Cell invasion and migration were determined by the transwell invasion assay and wound-healing assay. A nude mice xenograft tumor model was performed to investigate the biological function of HOXB-AS3 in vivo. Results: The results indicated that HOXB-AS3 was significantly elevated in gallbladder carcinoma tissues and cell lines. We used siHOXB-AS3 to knockdown the expression levels of HOXB-AS3. And knockdown HOXB-AS3 expression depressed gallbladder cancer cell viability and induced cell apoptosis. In addition, the gallbladder carcinoma cell cycle was obviously arrested at the G1 phase. Cell invasion and migration were markedly suppressed following knockdown HOXB-AS3 expression. Furthermore, the features of siHOXB-AS3 in gallbladder cancer cells could be reversed by the ERK1/2 phosphorylation agonist Ro 67-7476. Finally, we confirmed that HOXB-AS3 promoted the growth of transplanted tumors in vivo. Conclusion: HOXB-AS3 promoted gallbladder carcinoma cell proliferation, invasion and migration by activating the MEK/ERK signaling pathway. HOXB-AS3 contributed to gallbladder cancer tumorigenesis and metastasis, making it a viable therapeutic target for gallbladder cancer treatment.

RNA-protein interactions reveals the pivotal role of lncRNA1840 in tomato fruit maturation.

Long non-coding RNAs (lncRNAs) play crucial roles in various biological processes in plants. However, the functional mechanism of lncRNAs in fruit ripening, particularly the transition from unripe to ripe stages, remains elusive. One such lncRNA1840, reported by our group, was found to have important role in tomato fruit ripening. In the present study, we gain insight into its functional role in fruit ripening. CRISPR-Cas9 mediated lncRNA1840 mutants caused the delayed tomato fruit ripening. Notably, loss function of lncRNA1840 did not directly impact ethylene signaling but rather delay ethylene synthesis. Transcriptomic analysis revealed differences in the expression of ripening related genes in lncRNA1840 mutants, suggesting that it is involved in gene regulation of fruit ripening. We used Chromatin Isolation by RNA Purification (ChIRP)-Seq to identify lncRNA1840 binding sites on chromatin. ChIRP-seq suggested that lncRNA1840 had occupancy on 40 genes, but none of them is differentially expressed genes in transcriptomic analysis, which indicated lncRNA1840 might indirectly modulate the gene expression. ChIRP-mass spectrometry analysis identified potential protein interactors of lncRNA1840, Pre-mRNA processing splicing factor 8, highlighting its involvement in post-transcriptional regulatory pathways. In summary, lncRNA1840 is key player in tomato plant growth and fruit ripening, with multifaceted roles in gene expression and regulatory networks.

Intraindividual variability of semen quality, proteome, and sncRNA profiles in a healthy cohort of young adults.

BACKGROUND: Within-subject variability of semen parameters and molecular components of ejaculates in young men remains poorly understood. OBJECTIVES: To investigate intraindividual variability (IIV) of semen parameters and molecular markers in repeated ejaculates from young men. MATERIALS AND METHODS: Semen parameters were assessed in samples collected 6-8 days apart from 164 18-19-year old participants of the Russian Children's Study, a prospective cohort. Subsets of paired samples were used for label-free quantitation and targeted mass-spectrometry of proteins in seminal plasma (SP) and seminal extracellular vesicles (EVs), and for small non-coding RNA (sncRNA) profiling in EVs and spermatozoa using RNA-seq. The mean difference between two ejaculates, within-subject variation, intraclass correlation, and concordance correlation were used to assess IIV for all parameters. Low variability with high reproducibility and high reliability was considered if CVw < 15% and ICC > 0.90, respectively. RESULTS: Analytical variability was low for all investigated parameters in technical replicates. IIV was assessed for basic semen parameters and proteins in SPs and EVs: 319 and 777 proteins, respectively, using untargeted analysis; 9 and 10 proteins using targeted quantification. We also described the IIV for sncRNA, including microRNA, piwi-interacting RNA, tRNA, and tRNA-derived small RNA (tsRNA) in EVs (409 sncRNA and 78 tsRNA) and in spermatozoa (265 sncRNA and 15 tsRNA). We identified 22 and 27 non-overlapping proteins in SP and EVs, respectively, and 46 and 9 sncRNA, including 5 and 0 tsRNA in seminal EVs and spermatozoa, respectively, with low variability. The fatty acid synthase (FAS) had the lowest IIV in both media in targeted protein quantification. DISCUSSION: We identified a number of proteins and sncRNA with low variability among 111 proteins, 176 sncRNA, and 12 tsRNA which were previously suggested as biomarkers of male fertility and reproductive outcomes: lactotransferrin, cysteine-rich secretory protein 3, alpha-1-antichymotrypsin, epididymal sperm-binding protein 1, glutathione S-transferase Mu 3, alpha-1-acid glycoprotein 2, serum amyloid P-component, aminopeptidase N, neprilysin, FAS, and miR-10b-3p, miR-122-5p, miR-205-5p, miR-222-3p, miR-34c-5p, miR-509-3-5p, miR-888-5p, miR-892a, miR-363-3p, miR-941, miR-146a-5p, miR-744-5p. CONCLUSION: These molecules have low IIV and may be promising candidate biomarkers of male fertility and reproductive health.

Clinical application value of long non-coding RNAs signatures of genomic instability in predicting prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) presents challenges due to its high recurrence and metastasis rates and poor prognosis. While current clinical diagnostic and prognostic indicators exist, their accuracy remains imperfect due to their biological complexity. Therefore, there is a quest to identify improved biomarkers for HCC diagnosis and prognosis. By combining long non-coding RNA (lncRNA) expression and somatic mutations, Duan et al identified five representative lncRNAs from 88 lncRNAs related to genomic instability (GI), forming a GI-derived lncRNA signature (LncSig). This signature outperforms previously reported LncSig and TP53 mutations in predicting HCC prognosis. In this editorial, we comprehensively evaluate the clinical application value of such prognostic evaluation model based on sequencing technology in terms of cost, time, and practicability. Additionally, we provide an overview of various prognostic models for HCC, aiding in a comprehensive understanding of research progress in prognostic evaluation methods.

Epigenetic insights into Fragile X Syndrome.

Fragile X Syndrome (FXS) is a genetic neurodevelopmental disorder closely associated with intellectual disability and autism spectrum disorders. The core of the disease lies in the abnormal expansion of the CGG trinucleotide repeat sequence at the 5'end of the FMR1 gene. When the repetition exceeds 200 times, it causes the silencing of the FMR1 gene, leading to the absence of the encoded Fragile X mental retardation protein 1 (FMRP). Although the detailed mechanism by which the CGG repeat expansion triggers gene silencing is yet to be fully elucidated, it is known that this process does not alter the promoter region or the coding sequence of the FMR1 gene. This discovery provides a scientific basis for the potential reversal of FMR1 gene silencing through interventional approaches, thereby improving the symptoms of FXS. Epigenetics, a mechanism of genetic regulation that does not depend on changes in the DNA sequence, has become a new focus in FXS research by modulating gene expression in a reversible manner. The latest progress in molecular genetics has revealed that epigenetics plays a key role in the pathogenesis and pathophysiological processes of FXS. This article compiles the existing research findings on the role of epigenetics in Fragile X Syndrome (FXS) with the aim of deepening the understanding of the pathogenesis of FXS to identify potential targets for new therapeutic strategies.

Transcriptomic analysis reveals interactive effects of polyvinyl chloride microplastics and cadmium on Mytilus galloprovincialis: Insights into non-coding RNA responses and environmental implications.

Despite increasing concerns regarding the interactions of microplastic and heavy metal pollution, there is limited knowledge on the molecular responses of marine organisms to these stressors. In this study, we used whole-transcriptome sequencing to investigate the molecular responses of the ecologically and economically important bivalve Mytilus galloprovincialis to individual and combined exposures of environmentally relevant concentrations of PVC microplastics and cadmium (Cd). Our results revealed distinct transcriptional changes in M. galloprovincialis, with significant overlap in the differentially expressed genes between the individual and combined exposure groups. Genes involved in cellular senescence, oxidative stress, and galactose metabolism were differentially expressed. Additionally, key signaling pathways related to apoptosis and drug metabolism were significantly modulated. Notably, the interaction of PVC microplastics and Cd resulted in differential expression of genes involved in drug metabolism and longevity regulating compared to single exposures. This suggests that the interaction between these two stressors may have amplified effects on mussel health. Overall, this comprehensive transcriptomic analysis provides valuable insights into the adaptive and detrimental responses of M. galloprovincialis to PVC microplastics and Cd in the environment.

lncRNA TUG1 transcript levels and psychological disorders: insights into interplay of glycemic index and glycemic load.

BACKGROUND: There is an association between obesity and psychological disorders such as depression, anxiety, and stress. Environmental factors and genetics play a crucial role in this regard. Several long non-coding RNAs (lncRNAs) are involved in the pathophysiology of the nervous system. Additionally, we intend to investigate how dietary glycemic index and load relate to psychological disorders in women with obesity and overweight by identifying the possible interaction with metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1). METHODS: 267 overweight or obese women between the ages of 18 and 48 were recruited for the current study. A reliable and validated food frequency questionnaire (FFQ) consisting of 147 items assessed food consumption, glycemic load (GL), and glycemic index (GI). Depression-Anxiety-Stress Scales (DASS-21) were used to assess mental well-being. A real-time polymerase chain reaction (PCR) was used to assess transcript levels for lncRNAs MALAT1 and TUG1. RESULTS: In obese and overweight women, a positive correlation was found between anxiety and MALAT1 mRNA levels (P = 0.007, CC = 0.178). Age, energy intake, physical activity, total fat, income, marriage, thyroid, and BMI were adjusted, and GI and TUG1 were positively correlated on DASS-21 (ß = 0.006, CI = 0.001, 0.01, P = 0.031), depression (ß = 0.002, CI = 0.001, 0.004, P = 0.019), Stress (ß = 0.003, CI = 0.001, 0.005, P = 0.027). The interaction of GL and TUG1 on stress was also observed (ß = 0.03, CI = 0.001, 0.07, P = 0.048). CONCLUSIONS: The lncRNA TUG1 appears to be associated with depression and stress through interaction with GI and correlated with stress by interaction with GL. To establish this concept, further research is required.

A ligation-independent sequencing method reveals tRNA-derived RNAs with blocked 3' termini.

Despite the numerous sequencing methods available, the diversity in RNA size and chemical modification makes it difficult to capture all RNAs in a cell. We developed a method that combines quasi-random priming with template switching to construct sequencing libraries from RNA molecules of any length and with any type of 3' modifications, allowing for the sequencing of virtually all RNA species. Our ligation-independent detection of all types of RNA (LIDAR) is a simple, effective tool to identify and quantify all classes of coding and non-coding RNAs. With LIDAR, we comprehensively characterized the transcriptomes of mouse embryonic stem cells, neural progenitor cells, mouse tissues, and sperm. LIDAR detected a much larger variety of tRNA-derived RNAs (tDRs) compared with traditional ligation-dependent sequencing methods and uncovered tDRs with blocked 3' ends that had previously escaped detection. Therefore, LIDAR can capture all RNAs in a sample and uncover RNA species with potential regulatory functions.