Implications Of lncRNAs Research Articles

Implications of lncRNAs in Helicobacter pylori-associated gastrointestinal cancers: underlying mechanisms and future perspectives.

Helicobacter pylori (H. pylori) is a harmful bacterium that is difficult to conveniently diagnose and effectively eradicate. Chronic H. pylori infection increases the risk of gastrointestinal diseases, even cancers. Despite the known findings, more underlying mechanisms are to be deeply explored to facilitate the development of novel prevention and treatment strategies of H. pylori infection. Long noncoding RNAs (lncRNAs) are RNAs with more than 200 nucleotides. They may be implicated in cell proliferation, inflammation and many other signaling pathways of gastrointestinal cancer progression. The dynamic expression of lncRNAs indicates their potential to be diagnostic or prognostic biomarkers. In this paper, we comprehensively summarize the processes of H. pylori infection and the treatment methods, review the known findings of lncRNA classification and functional mechanisms, elucidate the roles of lncRNAs in H. pylori-related gastrointestinal cancer, and discuss the clinical perspectives of lncRNAs.

BCLncRDB: a comprehensive database of LncRNAs associated with breast cancer.

Breast cancer, the most common cancer in women, is characterized by high morbidity and mortality worldwide. Recent evidence has shown that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of breast cancer. However, despite increasing data and evidence indicating the implication of lncRNAs in breast cancer, no web resource or database exists primarily for lncRNAs associated with only breast cancer. Therefore, we developed a manually curated, comprehensive database, "BCLncRDB," for lncRNAs associated with breast cancer. For this, we collected, processed, and analyzed available data on breast cancer-associated lncRNAs from different sources, including previously published research articles, the Gene Expression Omnibus (GEO) Database of the National Centre for Biotechnology Information (NCBI), The Cancer Genome Atlas (TCGA), and the Ensembl database; subsequently, these data were hosted at BCLncRDB for public access. Currently, the database contains 5324 unique breast cancer-lncRNA associations and has the following features: (i) a user-friendly, easy-to-use web interface for searching and browsing about lncRNAs of the user's interest, (ii) differentially expressed and methylated lncRNAs, (iii) stage- and subtype-specific lncRNAs, and (iv) drugs, subcellular localization, sequence, and chromosome information of these lncRNAs. Thus, the BCLncRDB provides a one-stop dedicated platform for exploring breast cancer-related lncRNAs to advance and support the ongoing research on this disease. The BCLncRDB is publicly available for use at http://sls.uohyd.ac.in/new/bclncrdb_v1 .

Emerging role of lncRNAs in drug resistance mechanisms in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) originates in the squamous cell lining the mucosal surfaces of the head and neck region, including the oral cavity, nasopharynx, tonsils, oropharynx, larynx, and hypopharynx. The heterogeneity, anatomical, and functional characteristics of the patient make the HNSCC a complex and difficult-to-treat disease, leading to a poor survival rate and a decreased quality of life due to the loss of important physiologic functions and aggressive surgical injury. Alteration of driver-oncogenic and tumor-suppressing lncRNAs has recently been recently in HNSCC to obtain possible biomarkers for diagnostic, prognostic, and therapeutic approaches. This review provides current knowledge about the implication of lncRNAs in drug resistance mechanisms in HNSCC. Chemotherapy resistance is a major therapeutic challenge in HNSCC in which lncRNAs are implicated. Lately, it has been shown that lncRNAs involved in autophagy induced by chemotherapy and epithelial–mesenchymal transition (EMT) can act as mechanisms of resistance to anticancer drugs. Conversely, lncRNAs involved in mesenchymal–epithelial transition (MET) are related to chemosensitivity and inhibition of invasiveness of drug-resistant cells. In this regard, long non-coding RNAs (lncRNAs) play a pivotal role in both processes and are important for cancer detection, progression, diagnosis, therapy response, and prognostic values. As the involvement of more lncRNAs is elucidated in chemoresistance mechanisms, an improvement in diagnostic and prognostic tools could promote an advance in targeted and specific therapies in precision oncology.

GEE-TGDR: A Longitudinal Feature Selection Algorithm and Its Application to lncRNA Expression Profiles for Psoriasis Patients Treated with Immune Therapies.

With the fast evolution of high-throughput technology, longitudinal gene expression experiments have become affordable and increasingly common in biomedical fields. Generalized estimating equation (GEE) approach is a widely used statistical method for the analysis of longitudinal data. Feature selection is imperative in longitudinal omics data analysis. Among a variety of existing feature selection methods, an embedded method—threshold gradient descent regularization (TGDR)—stands out due to its excellent characteristics. An alignment of GEE with TGDR is a promising area for the purpose of identifying relevant markers that can explain the dynamic changes of outcomes across time. We proposed a new novel feature selection algorithm for longitudinal outcomes—GEE-TGDR. In the GEE-TGDR method, the corresponding quasilikelihood function of a GEE model is the objective function to be optimized, and the optimization and feature selection are accomplished by the TGDR method. Long noncoding RNAs (lncRNAs) are posttranscriptional and epigenetic regulators and have lower expression levels and are more tissue-specific compared with protein-coding genes. So far, the implication of lncRNAs in psoriasis remains largely unexplored and poorly understood even though some evidence in the literature supports that lncRNAs and psoriasis are highly associated. In this study, we applied the GEE-TGDR method to a lncRNA expression dataset that examined the response of psoriasis patients to immune treatments. As a result, a list including 10 relevant lncRNAs was identified with a predictive accuracy of 70% that is superior to the accuracies achieved by two competitive methods and meaningful biological interpretation. A widespread application of the GEE-TGDR method in omics longitudinal data analysis is anticipated.

Long Non-Coding RNAs in Neuronal Aging.

The expansion of long non-coding RNAs (lncRNAs) in organismal genomes has been associated with the emergence of sophisticated regulatory networks that may have contributed to more complex neuronal processes, such as higher-order cognition. In line with the important roles of lncRNAs in the normal functioning of the human brain, dysregulation of lncRNA expression has been implicated in aging and age-related neurodegenerative disorders. In this paper, we discuss the function and expression of known neuronal-associated lncRNAs, their impact on epigenetic changes, the contribution of transposable elements to lncRNA expression, and the implication of lncRNAs in maintaining the 3D nuclear architecture in neurons. Moreover, we discuss how the complex molecular processes that are orchestrated by lncRNAs in the aged brain may contribute to neuronal pathogenesis by promoting protein aggregation and neurodegeneration. Finally, this review explores the possibility that age-related disturbances of lncRNA expression change the genomic and epigenetic regulatory landscape of neurons, which may affect neuronal processes such as neurogenesis and synaptic plasticity.

Angio-LncRs: LncRNAs that regulate angiogenesis and vascular disease.

Long noncoding RNAs (lncRNAs) represent a large subgroup of RNAs that are longer than 200 nucleotides and have no apparent protein coding potential. They have diverse functions in different biological processes by regulating chromatin remodeling or protein translation. This review summarizes the recent progress of lncRNAs in angiogenesis and vascular diseases. A general overview of lncRNA functional mechanisms will be introduced. A list of lncRNAs, which are termed “Angio-LncRs”, including MALAT1, MANTIS, PUNISHER, MEG3, MIAT, SENCR and GATA6-AS, will be discussed regarding their expression, regulation, function and mechanism of action in angiogenesis. Implications of lncRNAs in vascular diseases, such as atherosclerosis, hypertension, vascular retinopathies and tumor angiogenesis will also be discussed.

Genome-wide analysis of aberrantly expressed lncRNAs and miRNAs with associated co-expression and ceRNA networks in β-thalassemia and hereditary persistence of fetal hemoglobin.

The implications of lncRNAs regarding fetal hemoglobin (HbF) induction in hemoglobin disorders remain poorly understood. In this study, microarray analysis was performed to profile lncRNAs, miRNAs and mRNAs in individuals with hereditary persistence of fetal hemoglobin (HPFH), β-thalassemia carriers with high HbF levels and healthy controls. The results show aberrant expression of 862 lncRNAs, 568 mRNAs and 63 miRNAs in the high-HbF group compared with the control group. Altered NR_001589, NR_120526, T315543, miR-486-3p, miR-19b-1-5p and miR-20a-3p expression was confirmed by quantitative reverse transcription-polymerase chain reaction, and Spearman correlation coefficients revealed significant positive correlations with HbF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed the hematopoietic cell lineage and apoptosis to be most significantly dysregulated in HbF induction. We analyzed coding genes near the lncRNAs and constructed a coding-noncoding co-expression network. Based on the results, lncRNAs likely contribute to increased HbF levels by activating expression of HBE1 and hematopoietic cell lineage-inducible molecules and by inhibiting that of apoptosis-inducible molecules. Finally, through construction of a competing endogenous RNA network, we found that 6 lncRNAs could bind competitively with miR-486-3p, resulting in increased HbF levels. Taken together, our findings provide new insights into the mechanisms of HbF induction and potentially provide new targets for the treatment of β-thalassemia major.

Implication of lncRNAs in pathogenesis of esophageal cancer.

Long non-coding RNAs (lncRNAs), transcripts as longer than 200 nt in length with a great number of varieties in human genomics, play important roles in the regulation of genetics and epigenetics including gene transcription and post-transcription. Increasing evidence have demonstrated the upregulation of lncRNAs in tumorigenesis and metastasis of esophageal cancer (EC), a type of malignant tumors particularly in Asia. In this review, we briefly discuss the profiles and functions of lncRNAs involved in the progression of EC, which may provide a new approach to improve EC diagnosis and treatment.