Annotation and curation of the causality information in LncRNADisease

Abstract Disease causative non-coding RNAs (ncRNAs) are of great importance in understanding a disease, for they directly contribute to the development or progress of a disease. Identifying the causative ncRNAs can provide vital implications for biomedical researches. In this work, we updated the long non-coding RNA disease database (LncRNADisease) with long non-coding RNA (lncRNA) causality information with manual annotations of the causal associations between lncRNAs/circular RNAs (circRNAs) and diseases by reviewing related publications. Of the total 11 568 experimental associations, 2297 out of 10 564 lncRNA-disease associations and 198 out of 1004 circRNA-disease associations were identified to be causal, whereas 635 lncRNAs and 126 circRNAs were identified to be causative for the development or progress of at least one disease. The updated information and functions of the database can offer great help to future researches involving lncRNA/circRNA-disease relationship. The latest LncRNADisease database is available at http://www.rnanut.net/lncrnadisease.

Download Full-text

Long Non-coding RNA FEZF1-AS1 Promotes Growth and Reduces Apoptosis Through Regulation of miR-363-3p/PAX6 Axis in Retinoblastoma

Biochemical Genetics ◽

10.1007/s10528-020-10026-7 ◽

2021 ◽

Author(s):

Xiuming Liu ◽

Xiaofeng Li ◽

Jianchang Li

Keyword(s):

Cell Viability ◽

Antisense Rna ◽

Tumor Formation ◽

Retinoblastoma Cell ◽

Non Coding Rna ◽

High Incidence ◽

Non Coding Rnas ◽

Long Non Coding Rna ◽

Common Malignancy

AbstractRetinoblastoma is the most common malignancy in children's eyes with high incidence. Long non-coding RNAs (lncRNAs) play important roles in the progression of retinoblastoma. LncRNA FEZF1 antisense RNA 1 (FEZF1-AS1) has been found to stimulate retinoblastoma. However, the mechanism of FEZF1-AS1 underlying progression of retinoblastoma is still unclear. In current study, FEZF1-AS1 was up-regulated in retinoblastoma tissues and cells. FEZF1-AS1 overexpression enhanced retinoblastoma cell viability, promoted cell cycle, and inhibited apoptosis. Conversely, FEZF1-AS1 knockdown reduced cell viability, cycle, and elevated apoptosis. The interaction between FEZF1-AS1 and microRNA-363-3p (miR-363-3p) was confirmed. FEZF1-AS1 down-regulated miR-363-3p and up-regulated PAX6. PAX6 was a target gene of miR-363-3p. EZF1-AS1 promoted retinoblastoma cell viability and suppressed apoptosis via PAX6. Further, we demonstrated that FEZF1-AS1 contribute to tumor formation in vivo. In conclusion, FEZF1-AS1 elevated growth and inhibited apoptosis by regulating miR-363-3p/PAX6 in retinoblastoma, which provide a new target for retinoblastoma treatment.

Download Full-text

Integrated Analysis of Long Non-Coding RNA and mRNA Expression Profiles in Testes of Calves and Sexually Mature Wandong Bulls (Bos taurus)

Animals ◽

10.3390/ani11072006 ◽

2021 ◽

Vol 11 (7) ◽

pp. 2006

Author(s):

Hongyu Liu ◽

Ibrar Muhammad Khan ◽

Huiqun Yin ◽

Xinqi Zhou ◽

Muhammad Rizwan ◽

...

Keyword(s):

Target Genes ◽

Expression Profiles ◽

Age Groups ◽

Adherens Junction ◽

Integrated Analysis ◽

Sequencing Data ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Rna Interaction ◽

Long Non Coding Rna

The mRNAs and long non-coding RNAs axes are playing a vital role in the regulating of post-transcriptional gene expression. Thereby, elucidating the expression pattern of mRNAs and long non-coding RNAs underlying testis development is crucial. In this study, mRNA and long non-coding RNAs expression profiles were investigated in 3-month-old calves and 3-year-old mature bulls’ testes by total RNA sequencing. Additionally, during the gene level analysis, 21,250 mRNAs and 20,533 long non-coding RNAs were identified. As a result, 7908 long non-coding RNAs (p-adjust < 0.05) and 5122 mRNAs (p-adjust < 0.05) were significantly differentially expressed between the distinct age groups. In addition, gene ontology and biological pathway analyses revealed that the predicted target genes are enriched in the lysine degradation, cell cycle, propanoate metabolism, adherens junction and cell adhesion molecules pathways. Correspondingly, the RT-qPCR validation results showed a strong consistency with the sequencing data. The source genes for the mRNAs (CCDC83, DMRTC2, HSPA2, IQCG, PACRG, SPO11, EHHADH, SPP1, NSD2 and ACTN4) and the long non-coding RNAs (COX7A2, COX6B2, TRIM37, PRM2, INHBA, ERBB4, SDHA, ATP6VOA2, FGF9 and TCF21) were found to be actively associated with bull sexual maturity and spermatogenesis. This study provided a comprehensive catalog of long non-coding RNAs in the bovine testes and also offered useful resources for understanding the differences in sexual development caused by the changes in the mRNA and long non-coding RNA interaction expressions between the immature and mature stages.

Download Full-text

ADAMTS9-AS2: A functional long non-coding RNA in tumorigenesis

Current Pharmaceutical Design ◽

10.2174/1381612827666210325105106 ◽

2021 ◽

Vol 27 ◽

Author(s):

Wen Xu ◽

Bei Wang ◽

Yuxuan Cai ◽

Jinlan Chen ◽

Xing Lv ◽

...

Keyword(s):

Dna Methylation ◽

Signaling Pathways ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Human Cancer ◽

Migration Inhibition ◽

Cancer Proliferation ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Background: Long non-coding RNAs (lncRNA) have been identified as novel molecular regulators in cancers. LncRNA ADAMTS9-AS2 can mediate the occurrence and development of cancer through various ways such as regulating miRNAs, activating the classical signaling pathways in cancer, and so on, which have been studied by many scholars. In this review, we summarize the molecular mechanisms of ADAMTS9-AS2 in different human cancers. Methods: Through a systematic search of PubMed, lncRNA ADAMTS9-AS2 mediated molecular mechanisms in cancer are summarized inductively. Results: ADAMTS9-AS2 aberrantly expression in different cancers is closely related to cancer proliferation, invasion, migration, inhibition of apoptosis. The involvement of ADAMTS9-AS2 in DNA methylation, mediating PI3K / Akt / mTOR signaling pathways, regulating miRNAs and proteins, and such shows its significant potential as a therapeutic cancer target. Conclusion: LncRNA ADAMTS9-AS2 can become a promising biomolecular marker and a therapeutic target for human cancer.

Download Full-text

Non-Coding RNA in Acute Ischemic Stroke: Mechanisms, Biomarkers and Therapeutic Targets

Cell Transplantation ◽

10.1177/0963689718806818 ◽

2018 ◽

Vol 27 (12) ◽

pp. 1763-1777 ◽

Cited By ~ 15

Author(s):

Sheng-Wen Wang ◽

Zhong Liu ◽

Zhong-Song Shi

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Neural Development ◽

Therapeutic Targets ◽

Circular Rnas ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Cerebral Ischemic ◽

Functional Rnas ◽

The Brain

Non-coding RNAs (ncRNAs) are a class of functional RNAs that regulate gene expression in a post-transcriptional manner. NcRNAs include microRNAs, long non-coding RNAs and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes, including cerebral ischemic injury, neurodegeneration, neural development, and plasticity. Stroke is one of the leading causes of death and physical disability worldwide. Acute ischemic stroke (AIS) occurs when brain blood flow stops, and that stoppage results in reduced oxygen and glucose supply to cells in the brain. In this article, we review the latest progress on ncRNAs in relation to their implications in AIS, as well as their potential as diagnostic and prognostic biomarkers. We also review ncRNAs acting as possible therapeutic targets in future precision medicine. Finally, we conclude with a brief discussion of current challenges and future directions for ncRNAs studies in AIS, which may facilitate the translation of ncRNAs research into clinical practice to improve clinical outcome of AIS.

Download Full-text

Integrative Analysis of lncRNAs, miRNAs, and mRNA-Associated ceRNA Network in an Atopic Dermatitis Recurrence Model

International Journal of Molecular Sciences ◽

10.3390/ijms19103263 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3263 ◽

Cited By ~ 4

Author(s):

Xiaoyu Wang ◽

Kaifan Bao ◽

Peng Wu ◽

Xi Yu ◽

Can Wang ◽

...

Keyword(s):

Atopic Dermatitis ◽

Messenger Rna ◽

Integrative Analysis ◽

Ample Evidence ◽

Cerna Network ◽

Non Coding Rna ◽

Recurrence Model ◽

Non Coding Rnas ◽

Remission Phase ◽

Long Non Coding Rna

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence.

Download Full-text

Long-non Coding RNAs Related to Fat Deposition in Pigs Included lncRNA Corresponding to Human MALAT1

10.20944/preprints202103.0356.v1 ◽

2021 ◽

Author(s):

Katarzyna Piórkowska ◽

Kacper Żukowski ◽

Katarzyna Ropka-Molik ◽

Mirosław Tyra

Keyword(s):

Regulatory Elements ◽

Fat Deposition ◽

Differentially Expressed ◽

Rna Molecules ◽

Non Coding Rna ◽

Sequencing Method ◽

Non Coding Rnas ◽

Potential Interactions ◽

Long Non Coding Rna ◽

Generation Sequencing

Obesity is a problem in the last decades since the development of different technologies forced the submission of a faster pace of life, resulting in nutrition style changes. In turn, domestic pigs are an excellent animal model in recognition of adiposity-related processes, corresponding to the size of individual organs, the distribution of body fat in the organism, and similar metabolism. The present study applied the next-generation sequencing method to identify adipose tissue (AT) transcriptomic signals related to increased fat content by identifying differentially expressed genes (DEGs), included long-non coding RNA molecules. The Freiburg RNA tool was applied to recognise predicting hybridisation energy of RNA-RNA interactions. The results indicated several long non-coding RNAs (lncRNAs) whose expression was significantly positively or negatively associated with fat deposition. lncRNAs play an essential role in regulating gene expression by sponging miRNA, binding transcripts, facilitating translation, or coding other smaller RNA regulatory elements. In the pig fat tissue of obese group, increased expression of lncRNAs corresponding to human MALAT1 was observed that previously recognised in the obesity-related context. Moreover, hybridisation energy analyses pinpointed numerous potential interactions between identified differentially expressed lncRNAs, and obesity-related genes and miRNAs expressed in AT.

Download Full-text

Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.655157 ◽

2021 ◽

Vol 8 ◽

Author(s):

Bei-Yan Liu ◽

Lin Li ◽

Li-Wei Bai ◽

Chang-Shui Xu

Keyword(s):

Oxidative Stress ◽

Peripheral Neuropathy ◽

Schwann Cells ◽

Diabetic Peripheral Neuropathy ◽

Beclin 1 ◽

Diabetic Mice ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of XIST and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p (miR-30d-5p) was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of XIST could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of XIST was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the XIST overexpression could attenuate this result in the Schwann cells. Mechanically, XIST was able to sponge miR-30d-5p and miR-30d-5p-targeted SIRT1 in the Schwann cells. MiR-30d-5p inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. MiR-30d-5p mimic or SIRT1 depletion could reverse XIST overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that XIST attenuated DPN by inducing autophagy through miR-30d-5p/SIRT1 axis. XIST and miR-30d-5p may be applied as the potential targets for DPN therapy.

Download Full-text

Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

Bioscience Reports ◽

10.1042/bsr20191764 ◽

2020 ◽

Vol 40 (4) ◽

Cited By ~ 1

Author(s):

Chong Lu ◽

Xiuhua Wang ◽

Xiangwang Zhao ◽

Yue Xin ◽

Chunping Liu

Keyword(s):

Breast Cancer ◽

Normal Breast ◽

Tumor Promoter ◽

Women Health ◽

Non Coding Rna ◽

Non Coding Rnas ◽

And Migration ◽

Breast Tissues ◽

Long Non Coding Rna

Abstract Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.

Download Full-text

The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation

International Journal of Molecular Sciences ◽

10.3390/ijms22179165 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9165

Author(s):

David Roig-Carles ◽

Holly Jackson ◽

Katie F. Loveson ◽

Alan Mackay ◽

Rebecca L. Mather ◽

...

Keyword(s):

Large Family ◽

Diffuse Intrinsic Pontine Glioma ◽

Locked Nucleic Acid ◽

Normal Brain ◽

Pontine Glioma ◽

Incurable Cancer ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated H19 lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of H19 lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of H19 lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of H19 in DIPG cells. We found that H19 expression was higher in DIPG vs. normal brain tissue and other pedHGGs. H19 knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, H19 buffers let-7 microRNAs, resulting in the up-regulation of oncogenic let-7 target (e.g., SULF2 and OSMR). H19 is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer.

Download Full-text

Long Non-Coding RNA (lncRNA) in Oral Squamous Cell Carcinoma: Biological Function and Clinical Application

Cancers ◽

10.3390/cancers13235944 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5944

Author(s):

Jianfei Tang ◽

Xiaodan Fang ◽

Juan Chen ◽

Haixia Zhang ◽

Zhangui Tang

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Non Coding Rna ◽

Potential Applications ◽

Non Coding Rnas ◽

Long Non Coding Rna

Oral squamous cell carcinoma (OSCC) is a type of malignancy with high mortality, leading to poor prognosis worldwide. However, the molecular mechanisms underlying OSCC carcinogenesis have not been fully understood. Recently, the discovery and characterization of long non-coding RNAs (lncRNAs) have revealed their regulatory importance in OSCC. Abnormal expression of lncRNAs has been broadly implicated in the initiation and progress of tumors. In this review, we summarize the functions and molecular mechanisms regarding these lncRNAs in OSCC. In addition, we highlight the crosstalk between lncRNA and tumor microenvironment (TME), and discuss the potential applications of lncRNAs as diagnostic and prognostic tools and therapeutic targets in OSCC. Notably, we also discuss lncRNA-targeted therapeutic techniques including CRISPR-Cas9 as well as immune checkpoint therapies to target lncRNA and the PD-1/PD-L1 axis. Therefore, this review presents the future perspectives of lncRNAs in OSCC therapy, but more research is needed to allow the applications of these findings to the clinic.

Download Full-text