Mechanisms Of lncRNAs Research Articles

The long non-coding RNA GhlncRNA149.1 improves cotton defense response to aphid damage as a positive regulator

Long non-coding RNAs (lncRNAs) play crucial roles in various plant biological regulatory processes and defense responses to all sorts of biotic and abiotic stresses. However, there are limited studies on the function and mechanism of lncRNAs in plant defense responses to phytophagous insects. In this research, a lncRNA GhlncRNA149.1 was identified from upland cotton (Gossypium hirsutum L.). Depending on the position relationship between lncRNA and mRNA, we identified CC-NBS-LRR family gene GhA01G0129 as the target gene of GhlncRNA149.1. Expression levels of GhlncRNA149.1 and its target gene GhA01G0129 were significantly down-regulated in cotton cotyledons upon cotton aphid infestation. The expression level of GhlncRNA149.1 was significantly down-regulated after the induction of methyl jasmonate and salicylic acid, whereas expression level of its target gene GhA01G0129 was significantly up-regulated. Overexpression of GhlncRNA149.1 in cotton cotyledons enhanced the tolerance of cotton plants to cotton aphid feeding. Expectedly, silencing GhlncRNA149.1 increased susceptibility of cotton plants to cotton aphids. The expression level of GhA01G0129, the target gene of GhlncRNA149.1, was significantly up-regulated in cotton plants overexpressing GhlncRNA149.1, and significantly down-regulated in cotton plants silencing GhlncRNA149.1. The activity and expression levels of antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were up-regulated in cotton plants transiently overexpressing GhlncRNA149.1, while opposite results were obtained in cotton plants silencing GhlncRNA149.1. In addition, similar results were obtained in the expression levels of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), enhanced disease susceptibility 1 (EDS1) and non-expression of pathogenesis-related gene 1 (NPR1) in cotton plants transiently overexpressing GhlncRNA149.1 and silencing GhlncRNA149.1. These results collectively suggest that GhlncRNA149.1 improve the plant defense response to aphid attack, and thus has potential for enforcing cotton aphid prevention and control.

The exciting encounter between lncRNAs and radiosensitivity in IR-induced DNA damage events.

Radiation therapy is a commonly used tool in cancer management due to its ability to destroy malignant tumors. Mechanically, the efficacy of radiotherapy mainly depends on the inherent radiosensitivity of cancer cells and surrounding normal tissues, which mostly accounts for molecular dynamics associated with radiation-induced DNA damage. However, the relationship between radiosensitivity and DNA damage mechanism deserves to be further probed. As the well-established RNA regulators or effectors, long noncoding RNAs (lncRNAs) dominate vital roles in modulating ionizing radiation response by targeting crucial molecular pathways, including DNA damage repair. Recently, emerging evidence has constantly confirmed that overexpression or inhibition of lncRNAs can greatly influence the sensitivity of radiotherapy for many kinds of cancers, by driving a diverse array of DNA damage-associated signaling cascades. In conclusion, this review critically summarizes the recent progress in the molecular mechanism of IR-responsive lncRNAs in the context of radiation-induced DNA damage. The different response of lncRNAs when IR exposure. IR exposure can trigger the changes in expression pattern and subcellular localization of lncRNAs that influences the different radiology processes.

Long non-coding RNA H19: a potential biomarker and therapeutic target in human malignant tumors.

Long non-coding RNAs play important roles in cellular functions and disease development. H19, as a long non-coding RNA, is pervasively over-expressed in almost all kinds of human malignant tumors. Although many studies have reported that H19 is closely associated with tumor cell proliferation, apoptosis, invasion, metastasis, and chemoresistance, the role and mechanism of H19 in gene regulation and tumor development are largely unclear. In this review, we summarized the recent progress in the study of the major functions and mechanisms of H19 lncRNA in cancer development and progression. H19 possesses both oncogenic and tumor-suppressing activities, presumably through regulating target gene transcription, mRNA stability and splicing, and competitive inhibition of endogenous RNA degradation. Studies indicate that H19 may involve in cell proliferation and apoptosis, tumor initiation, migration, invasion, metastasis and chemoresistance and may serve as a potential biomarker for early diagnosis, prognosis, and novel molecular target for cancer therapy.

LncRNA 148400 Promotes the Apoptosis of Renal Tubular Epithelial Cells in Ischemic AKI by Targeting the miR-10b-3p/GRK4 Axis.

Although recent studies have reported that long non-coding RNA (lncRNA) is involved in the development of ischemic acute kidney injury (AKI), the exact function and regulatory mechanism of lncRNAs in ischemic AKI remain largely unknown. Herein, we found that ischemic injury promoted the expression of lncRNA 148400 in mouse proximal tubule-derived cell line (BUMPT) and C57BL/6J mice. Furthermore, the lncRNA148400 mediates ischemic injury-induced apoptosis of BUMPT cells. Mechanistically, lncRNA 148400 sponged miR-10b-3p to promote apoptosis via GRK4 upregulation. Finally, knockdown of lncRNA 148400 alleviated the I/R-induced deterioration of renal function, renal tubular injury, and cell apoptosis. In addition, cleaved caspase-3 is increased via targeting the miR-10b-3p/GRK4 axis. Collectively, these results showed that lncRNA 148400/miR-10b-3p/GRK4 axis mediated the development of ischemic AKI.

New Insights into lncRNAs in Aβ Cascade Hypothesis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia, but its pathogenesis is not fully understood, and effective drugs to treat or reverse the progression of the disease are lacking. Long noncoding RNAs (lncRNAs) are abnormally expressed and deregulated in AD and are closely related to the occurrence and development of AD. In addition, the high tissue specificity and spatiotemporal specificity make lncRNAs particularly attractive as diagnostic biomarkers and specific therapeutic targets. Therefore, an in-depth understanding of the regulatory mechanisms of lncRNAs in AD is essential for developing new treatment strategies. In this review, we discuss the unique regulatory functions of lncRNAs in AD, ranging from Aβ production to clearance, with a focus on their interaction with critical molecules. Additionally, we highlight the advantages and challenges of using lncRNAs as biomarkers for diagnosis or therapeutic targets in AD and present future perspectives in clinical practice.

LncRNA FPASL suppresses fibroblast proliferation through its DNA methylation via DNMT3b in hypertrophic scar.

Long noncoding RNAs (lncRNAs) are increasingly being implicated as key regulators of cell proliferation, apoptosis, and differentiation. However, the molecular mechanisms of specific lncRNAs in the context of hypertrophic scar remain largely unclear. Here, we find that the lncRNA FPASL (fibroblast proliferation-associated LncRNA) is downregulated in HS, and FPASL reduces fibroblast proliferation and colony formation and blocks cell cycle progression. Using GO annotation enrichment analysis along with AZC (a specific inhibitor of DNA methylation), we identify that DNA methylation is responsible for downregulating FPASL in hypertrophic scar. Subsequent studies demonstrate that high expression of DNMT3b inhibits FPASL expression in HS. Mechanistic study reveals a significant increase in fibroblast proliferation after transfection with LNA-FPASL, which is further inhibited by knockdown of DNMT3b. Thus, our study reveals that DNMT3b mediates hypermethylation of the lncRNA FPASL promoter and the downregulation of lncRNA FPASL promotes fibroblast proliferation in hypertrophic scar.

The Common LncRNAs of Neuroinflammation-Related Diseases.

Spatio-temporal specific long noncoding RNAs (lncRNAs) play important regulatory roles not only in the growth and development of the brain but also in the occurrence and development of neurologic diseases. Generally, the occurrence of neurologic diseases is accompanied by neuroinflammation. Elucidation of the regulatory mechanisms of lncRNAs on neuroinflammation is helpful for the clinical treatment of neurologic diseases. This paper focuses on recent findings on the regulatory effect of lncRNAs on neuroinflammatory diseases and selects 10 lncRNAs that have been intensively studied to analyze their mechanism action. The clinical treatment status of lncRNAs as drug targets is also reviewed. SIGNIFICANCE STATEMENT: Gene therapies such as clustered regularly interspaced short palindrome repeats technology, antisense RNA technology, and RNAi technology are gradually applied in clinical treatment, and the development of technology is based on a large number of basic research investigations. This paper focuses on the mechanisms of lncRNAs regulation of neuroinflammation, elucidates the beneficial or harmful effects of lncRNAs in neurosystemic diseases, and provides theoretical bases for lncRNAs as drug targets.

LINC01608 activated by YY1 facilitate hepatocellular carcinoma progression by modulating the EGFR/ERK axis.

Long non-coding RNAs (LncRNAs) have been demonstrated to associate with a variety of cancers. However, the mechanisms of LncRNAs in hepatocellular carcinoma (HCC) progression are still not fully clarified. LINC01608 expression level in HCC and adjacent normal tissues was detected by real-time-quantitively PCR (RT-qPCR) in clinical samples and in situ hybridization (ISH) in tissue microarray. Several functional assays were performed to determine the biological effects of LINC01608 in HCC cells in vitro, while subcutaneous xenograft models and lung metastasis models in nude mice and immunohistochemistry (IHC) results showed the role of LINC01608 in HCC progression in vivo. The combination of LINC01608 with miR-875-5p and target genes was elucidated by dual-luciferase report assays, RNA immunoprecipitation (RIP) assays and fluorescence in situ hybridization (FISH) assays. Finally, bioinformatics analysis and chromatin immunoprecipitation (CHIP) were performed to investigate the mechanism of Yin Yang-1 (YY1) regulating LINC01608 transcription. LINC01608 was overexpressed in HCC tissues, and high LINC01608 expression predicted poor overall survival (OS) and disease-free survival (DFS) in HCC patients. LINC01608 could promote HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated that LINC01608 could sponge to miR-875-5p and activate the EGFR/ERK pathway. Moreover, we identified transcriptional factor YY1 could bind to the promoter of LINC01608 and induce its transcription. LINC01608 could serve as a promising prognostic biomarker of HCC. YY1-activated LINC01608 could promote HCC progression by associating with miR-875-5p to induce the EGFR/ERK signalling pathway. This discovery might provide therapeutic strategies for HCC.

Knockdown of lncRNA XIST Ameliorates IL-1β-Induced Apoptosis of HUVECs and Change of Tissue Factor Level via miR-103a-3p/HMGB1 Axis in Deep Venous Thrombosis by Regulating the ROS/NF-κB Signaling Pathway.

The effect of lncRNA X inactive-specific transcript (XIST) inducing cardiovascular diseases on deep vein thrombosis (DVT) and its mechanism has not been reported. In this study, we uncovered the mystery that lncRNA XIST causes DVT with HUVEC dysfunction. The expression levels of lncRNA XIST and miR-103a-3p were detected by qRT-PCR, and HMGB1 expression was determined by qRT-PCR and western blot. The correlations among the expression levels of lncRNA XIST, miR-103a-3p, and HMGB1 were determined by Spearman's rank-order correlation test. XIST siRNA (si-XIST) was transfected into HUVECs to knock down the intrinsic expression of lncRNA XIST. The influences of si-XIST on interleukin-1 beta- (IL-1β-) treated HUVEC viability and apoptosis and the level of tissue factor (TF) were detected by MTT, flow cytometry, and ELISA kit, respectively. The relationships between lncRNA XIST, miR-103a-3p, and HMGB1 were predicted by the Encyclopedia of RNA Interactomes (ENCORI) database and verified by dual luciferase reporter assay. The effects of lncRNA XIST and miR-103a-3p on HMGB1 expression were detected by qRT-PCR, western blot, and immunofluorescence analysis. The levels of ROS/NF-κB pathway-related proteins were detected to study the regulatory mechanism of lncRNA XIST/miR-103a-3p/HMGB1 on IL-1β-treated HUVECs apoptosis and change of TF level. The upregulated expression levels of lncRNA XIST and HMGB1 and downregulated level of miR-103a-3p were found in the plasma of DVT patients and IL-1β-treated HUVECs. Si-XIST promoted cell viability and inhibited HUVEC apoptosis and ameliorated the change of TF level triggered by IL-1β. lncRNA XIST sponged miR-103a-3p and miR-103a-3p targeted HMGB1. Si-XIST inhibited the ROS/NF-κB pathway to suppress HUVEC apoptosis and ameliorate the change of TF level induced by IL-1β via the miR-103a-3p/HMGB1 axis. lncRNA XIST sponged miR-103a-3p improving HMGB1 expression to exacerbate DVT by activating the ROS/NF-κB signaling pathway. Our findings indicated that lncRNA XIST can be used as a potential therapeutic target in DVT.

Transcriptome-Wide Study of mRNAs and lncRNAs Modified by m6A RNA Methylation in the Longissimus Dorsi Muscle Development of Cattle-Yak.

Cattle-yak is a hybrid F1 generation of cattle and yak, which has a history of more than 3000 years and has shown better production performance and higher economic benefits than those of yaks. However, up to now, there has been no study on the transcriptome-wide m6A methylation profile of bovine skeletal muscle and its potential biological function during muscle development. Here, we observed significant changes in the expression levels of muscle-related marker genes and methylation-related enzymes during the development of cattle-yak, and the overall m6A content in the Longissimus dorsi muscle of 18-month-old cattle-yak decreased significantly. A total of 36,602 peaks, 11,223 genes and 8388 lncRNAs were identified in the two groups, including 2989 differential peaks (427 up-regulated peaks and 2562 down-regulated peaks), 1457 differentially expressed genes (833 up-regulated genes and 624 down-regulated genes) and 857 differentially expressed lncRNAs (293 up-regulated lncRNAs and 564 down-regulated lncRNAs). GO and KEGG analysis revealed that they were significantly enriched in some muscle-related pathways (Wnt signaling pathway and MAPK signaling pathway) and high-altitude adaptation-related pathway (HIF-1 signaling pathway). Moreover, m6A abundance was positively correlated with gene expression levels, while it was negatively correlated with lncRNA expression levels. This indicates that m6A modification played an important role in the Longissimus dorsi muscle development of cattle-yak; however, the regulation mechanism of m6A-modified mRNA and lncRNA may be different. This study was the first report of transcriptome-wide m6A-modified mRNAs and lncRNAs atlas in the Longissimus dorsi muscle development of cattle-yak, one which will provide new perspectives for genetic improvement in bovines.

Role of Long Noncoding RNAs in the Regulation of Cellular Immune Response and Inflammatory Diseases.

Long noncoding RNAs (lncRNAs) are recently discovered genetic regulatory molecules that regulate immune responses and are closely associated with the occurrence and development of various diseases, including inflammation, in humans and animals. Under specific physiological conditions, lncRNA expression varies at the cell or tissue level, and lncRNAs can bind to specific miRNAs, target mRNAs, and target proteins to participate in certain processes, such as cell differentiation and inflammatory responses, via the corresponding signaling pathways. This review article summarizes the regulatory role of lncRNAs in macrophage polarization, dendritic cell differentiation, T cell differentiation, and endothelial and epithelial inflammation. In addition, it describes the molecular mechanism of lncRNAs in acute kidney injury, hepatitis, inflammatory injury of the lung, osteoarthritis, mastitis, and neuroinflammation to provide a reference for the molecular regulatory network as well as the genetic diagnosis and treatment of inflammatory diseases in humans and animals.

The mechanism of lncRNAs in the crosstalk between epithelial-mesenchymal transition and tumor microenvironment for early colon adenocarcinoma based on molecular subtyping.

A large number of colon adenocarcinoma (COAD) patients are already advanced when diagnosed. In this study, we aimed to further understand the mechanism of tumor development in early COAD by focusing on epithelial-mesenchymal transition (EMT) and long non-coding RNAs (lncRNAs). Expression profiles of early COAD patients were obtained from public databases. EMT-related lncRNAs were used as a basis for constructing molecular subtypes through unsupervised consensus clustering. Genomic features, pathways and tumor microenvironment (TME) were compared between two subtypes. LncATLAS database was applied to analyze the relation between lncRNAs and transcription factors (TFs). First order partial correlation analysis was conducted to identify key EMT-related lncRNAs.C1 and C2 subtypes with distinct prognosis were constructed. Oncogenic pathways such as EMT, KRAS signaling, JAK-STAT signaling, and TGF-β signaling were significantly enriched in C2 subtype. Higher immune infiltration and expression of immune checkpoints were also observed in C2 subtype, suggesting the key EMT-related lncRNAs may play a critical role in the modulation of TME. In addition, JAK-STAT signaling pathway was obviously enriched in upregulated TFs in C2 subtype, which indicated a link between key lncRNAs and JAK-STAT signaling that may regulate TME. The study further expanded the research on the role of EMT-related lncRNAs in the early COAD. The six identified EMT-related lncRNAs could serve as biomarkers for early screening COAD.

Identification of novel antisense long non-coding RNA APMAP-AS that modulates porcine adipogenic differentiation and inflammatory responses

Long non-coding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation, fat metabolism and gene expression. However, the functional roles and mechanisms of lncRNAs in these processes remain unclear. Here, we identified a novel antisense transcript, named APMAP-AS, transcribed from adipocyte membrane-associated protein (APMAP) in the pig genome. APMAP-AS and APMAP were highly expressed in retroperitoneal adipose of obese pigs, compared with that in control pigs. Using a bone mesenchymal stem cells (BMSCs) adipogenic differentiation model, we found that APMAP-AS positively regulated adipogenic differentiation. APMAP-AS had the potential to form an RNA–RNA duplex with APMAP, and increased the stability of APMAP mRNA. Additionally, APMAP-AS promoted lipid metabolism and inhibited the expression of inflammatory factors. These findings of a natural antisense transcript for a regulatory gene associated with lipid synthesis might further our understanding of lncRNAs in driving adaptive adipose tissue remodeling and preserving metabolic health.

Long noncoding RNA DLGAP1-AS2 promotes tumorigenesis and metastasis by regulating the Trim21/ELOA/LHPP axis in colorectal cancer

BackgroundLong noncoding RNAs (lncRNAs) have driven research focused on their effects as oncogenes or tumor suppressors involved in carcinogenesis. However, the functions and mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear.MethodsThe expression of DLGAP1-AS2 was assessed by quantitative RT-PCR in multiple CRC cohorts. The impacts of DLGAP1-AS2 on CRC growth and metastasis were evaluated by a series of in vitro and in vivo assays. Furthermore, the underlying mechanism of DLGAP1-AS2 in CRC was revealed by RNA pull down, RNA immunoprecipitation, RNA sequencing, luciferase assays, chromatin immunoprecipitation, and rescue experiments.ResultsWe discovered that DLGAP1-AS2 promoted CRC tumorigenesis and metastasis by physically interacting with Elongin A (ELOA) and inhibiting its protein stability by promoting tripartite motif containing 21 (Trim21)-mediated ubiquitination modification and degradation of ELOA. In particular, we revealed that DLGAP1-AS2 decreases phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) expression by inhibiting ELOA-mediated transcriptional activating of LHPP and thus blocking LHPP-dependent suppression of the AKT signaling pathway. In addition, we also demonstrated that DLGAP1-AS2 was bound and stabilized by cleavage and polyadenylation specificity factor (CPSF2) and cleavage stimulation factor (CSTF3).ConclusionsThe discovery of DLGAP1-AS2, a promising prognostic biomarker, reveals a new dimension into the molecular pathogenesis of CRC and provides a prospective treatment target for this disease.

Knockdown of lncRNA HOXD-AS2 Improves the Prognosis of Glioma Patients by Inhibiting the Proliferation and Migration of Glioma Cells.

Increasing studies reported that long noncoding RNAs are involved in regulating glioma progression. However, the specific roles and mechanisms of lncRNAs in glioma remain unclear. Here, we sought to explore the functions of HOXD-AS2 in glioma progression. Gene expressions of lncRNAs in 5 normal brain tissue specimens and 5 glioblastoma tissue specimens were detected by gene expression profile chip technology. Bioinformatic analysis was performed to see whether differential expression of lncRNAs played any significant role in glioma occurrence and progression. The relationship between HOXD-AS2 level and clinical prognosis of the patients was analyzed. HOXD-AS2 was specifically interfered with by siRNA technology to observe its effects on U251 cell growth, proliferation, apoptosis, and invasion. The expression level of HOXD-AS2 gene in glioma was significantly higher than that in the normal brain tissue, which was related to the tumor grade. The level of HOXD-AS2 gene in patients with high-grade glioma was higher than that in patients with low-grade glioma. High expression of HOXD-AS2 gene was a risk factor for poor prognosis of glioma patients. Knocking down the expression of HOXD-AS2 in glioma cell line U251 arrested the cell cycle and reduced the cell proliferation. Furthermore, it could significantly reduce the migration ability of the cells but had no significant effect on the invasion. HOXD-AS2 is an oncogenic lncRNA associated with the poor prognosis of glioma. Knockdown of HOXD-AS2 may reduce the growth of glioma, which may provide a new avenue for treatment.

Cancer-associated fibroblasts-derived lncRNA signature as a putative biomarker in breast cancer.

Long noncoding RNAs (lncRNAs) have been reported to play a key role in regulating tumor microenvironment and immunity. Cancer-associated fibroblasts (CAFs) are abundant in many tumors. However, the functional and clinical significance of lncRNAs specifically expressed in CAFs has not been fully elucidated. In this study, we identified a list of 95 CAF-specific lncRNAs (FibLnc), including HHLA3, TP53TG1, ST7-AS1, LINC00536, ZNF503-AS1, MIR22HG, and MAPT-AS1, based on immune cell transcriptome expression profiling data. Based on the Cancer Genome Atlas and Gene Expression Omnibus datasets, we found that the FibLnc score predicted differences in overall patient survival and performed well in multiple datasets. FibLnc score was associated with the clinical stage of patients with breast cancer but did not significantly correlate with the PAM50 classification. Functional analysis showed that FibLnc was positively correlated with signaling pathways associated with malignant tumor progression. In addition, FibLnc was positively correlated with tumor mutational load and could predict immunotherapy response in patients with breast cancer receiving anti-PD-1 or anti-CTLA4 therapy. Our proposed FibLnc score was able to reflect the status of the immune environment and immunotherapeutic response in breast cancer, which could help explore potential therapeutic decisions and regulatory mechanisms of CAF-specific lncRNAs.

LncRNAs as biomarkers for predicting radioresistance and survival in cancer: a meta-analysis

The effect of long noncoding RNAs (lncRNAs) on the radiotherapy response has been gradually revealed. This systematic review and meta-analysis aimed to evaluate the association between the function and underlying mechanism of lncRNAs in regulating the radiosensitivity and radioresistance of different tumors. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to estimate the effect of lncRNAs on cancer patient prognosis, including overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS) and progression-free survival (PFS). Collectively, 23 lncRNAs in 11 cancer types were enrolled. Of them, 13 lncRNAs were downregulated and related to radiosensitivity, 11 lncRNAs were upregulated and related to radioresistance, and 3 lncRNAs were upregulated and related to radiosensitivity in cancers. Furthermore, 17 microRNAs and 20 pathways were targeted by different lncRNAs and contributed to the cancer radiotherapy response in this meta-analysis. The individual pooled HRs (95% CIs) of downregulated radiation-resistant and upregulated radiation-resistant lncRNAs for OS were 0.49 (0.40–0.60) and 1.88 (1.26–2.79), respectively. Our results showed that lncRNAs could modulate tumor radioresistance or sensitivity by affecting radiation-related signaling pathways and serve as potential biomarkers to predict radiotherapy response.

LncCMRR Plays an Important Role in Cardiac Differentiation by Regulating the Purb/Flk1 Axis.

As crucial epigenetic regulators, long noncoding RNAs (lncRNAs) play critical functions in development processes and various diseases. However, the regulatory mechanism of lncRNAs in early heart development is still limited. In this study, we identified cardiac mesoderm-related lncRNA (LncCMRR). Knockout (KO) of LncCMRR decreased the formation potential of cardiac mesoderm and cardiomyocytes during embryoid body differentiation of mouse embryonic stem (ES) cells. Mechanistic analyses showed that LncCMRR functionally interacted with the transcription suppressor PURB and inhibited its binding potential at the promoter region of Flk1, which safeguarded the transcription of Flk1 during cardiac mesoderm formation. We also carried out gene ontology term and signaling pathway enrichment analyses for the differentially expressed genes after KO of LncCMRR, and found significant correlation of LncCMRR with cardiac muscle contraction, dilated cardiomyopathy, and hypertrophic cardiomyopathy. Consistently, the expression level of Flk1 at E7.75 and the thickness of myocardium at E17.5 were significantly decreased after KO of LncCMRR, and the survival rate and heart function index of LncCMRR-KO mice were also significantly decreased as compared with the wild-type group. These findings indicated that the defects in early heart development led to functional abnormalities in adulthood heart of LncCMRR-KO mice. Conclusively, our findings elucidate the main function and regulatory mechanism of LncCMRR in cardiac mesoderm formation, and provide new insights into lncRNA-mediated regulatory network of mouse ES cell differentiation.

Finding lncRNA-Protein Interactions Based on Deep Learning With Dual-Net Neural Architecture.

The identification of lncRNA-protein interactions (LPIs) is important to understand the biological functions and molecular mechanisms of lncRNAs. However, most computational models are evaluated on a unique dataset, thereby resulting in prediction bias. Furthermore, previous models have not uncovered potential proteins (or lncRNAs) interacting with a new lncRNA (or protein). Finally, the performance of these models can be improved. In this study, we develop a Deep Learning framework with Dual-net Neural architecture to find potential LPIs (LPI-DLDN). First, five LPI datasets are collected. Second, the features of lncRNAs and proteins are extracted by Pyfeat and BioTriangle, respectively. Third, these features are concatenated as a vector after dimension reduction. Finally, a deep learning model with dual-net neural architecture is designed to classify lncRNA-protein pairs. LPI-DLDN is compared with six state-of-the-art LPI prediction methods (LPI-XGBoost, LPI-HeteSim, LPI-NRLMF, PLIPCOM, LPI-CNNCP, and Capsule-LPI) under four cross validations. The results demonstrate the powerful LPI classification performance of LPI-DLDN. Case study analyses show that there may be interactions between RP11-439E19.10 and Q15717, and between RP11-196G18.22 and Q9NUL5. The novelty of LPI-DLDN remains, integrating various biological features, designing a novel deep learning-based LPI identification framework, and selecting the optimal LPI feature subset based on feature importance ranking.

Integrated analysis of lncRNA and gene expression in longissimus dorsi muscle at two developmental stages of Hainan black goats.

It is deemed that meat quality of kids' is better than that of adults' for Hainan black goat. Generally, meat quality is affected by many indicators, such as intramuscular fat (IMF) content, muscle fiber diameter and shear force. It is indicated that long non-coding RNAs (lncRNAs) play essential roles in meat quality of goats. However, it is unclear whether and how lncRNAs and genes play their roles in meat quality of Hainan Black goats. Here, we firstly compared the meat quality between two-month-old kids (kids) and adult goats (adults). Then, the lncRNA-seq and RNA-seq data were integrated and analyzed to explore the potential functions of lncRNAs and genes. The results showed that adults' IMF content and muscle fiber diameter were extremely significantly higher than that of kids (P<0.01). For the sequenced data, average 84,970,398, and 83,691,250 clean reads were obtained respectively for Kids and adults, among which ~96% were mapped to the reference genome of goats. Through analyzing, 18,242 goat annotated genes, 1,429 goat annotated lncRNAs and 2,967 novel lncRNAs were obtained. Analysis of differential expression genes (DEGs) and lncRNAs (DELs) showed that 328 DEGs and 98 DELs existed between kids and adults. Furthermore, functional enrichment analysis revealed that a number of DEGs and DELs were mainly associated with IMF. Primarily, DGAT2 expressed higher in adults than that in kids and CPT1A expressed higher in kids than that in adults. Both of them were overlapped by DEGs and targets of DELs, suggesting the two DEGs and the DELs targeted by the two DEGs might be the potential regulators of goat IMF deposition. Taken together, our results provide basic support for further understanding the function and mechanism of lncRNAs and genes in meat quality of Hainan black goats.