Molecular Mechanisms Of lncRNAs Research Articles

Insights into the defensive roles of lncRNAs during Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae causes respiratory tract infections, affecting both children and adults, with varying degrees of severity ranging from mild to life-threatening. In recent years, a new class of regulatory RNAs called long non-coding RNAs (lncRNAs) has been discovered to play crucial roles in regulating gene expression in the host. Research on lncRNAs has greatly expanded our understanding of cellular functions involving RNAs, and it has significantly increased the range of functions of lncRNAs. In lung cancer, transcripts associated with lncRNAs have been identified as regulators of airway and lung inflammation in a process involving protein complexes. An excessive immune response and antibacterial immunity are closely linked to the pathogenesis of M. pneumoniae. The relationship between lncRNAs and M. pneumoniae infection largely involves lncRNAs that participate in antibacterial immunity. This comprehensive review aimed to examine the dysregulation of lncRNAs during M. pneumoniae infection, highlighting the latest advancements in our understanding of the biological functions and molecular mechanisms of lncRNAs in the context of M. pneumoniae infection and indicating avenues for investigating lncRNAs-related therapeutic targets.

Regulation of T cell differentiation and function by long noncoding RNAs in homeostasis and cancer.

Long noncoding RNAs (lncRNAs) increase in genomes of complex organisms and represent the largest group of RNA genes transcribed in mammalian cells. Previously considered only transcriptional noise, lncRNAs comprise a heterogeneous class of transcripts that are emerging as critical regulators of T cell-mediated immunity. Here we summarize the lncRNA expression landscape of different T cell subsets and highlight recent advances in the role of lncRNAs in regulating T cell differentiation, function and exhaustion during homeostasis and cancer. We discuss the different molecular mechanisms of lncRNAs and highlight lncRNAs that can serve as novel targets to modulate T cell function or to improve the response to cancer immunotherapies by modulating the immunosuppressive tumor microenvironment.

Epigenetically silenced lncRNA SNAI3-AS1 promotes ferroptosis in glioma via perturbing the m6A-dependent recognition of Nrf2 mRNA mediated by SND1

BackgroundFerroptosis has been linked to tumor progression and resistance to antineoplastic therapy. Long noncoding RNA (lncRNA) exerts a regulatory role in various biological processes of tumor cells, while the function and molecular mechanism of lncRNA in ferroptosis are yet to be clarified in glioma.MethodsBoth gain-of-function and loss-of-function experiments were employed to investigate the effects of SNAI3-AS1 on the tumorigenesis and ferroptosis susceptibility of glioma in vitro and in vivo. Bioinformatics analysis, Bisulfite sequencing PCR, RNA pull-down, RIP, MeRIP and dual-luciferase reporter assay were performed to explore the low expression mechanism of SNAI3-AS1 and the downstream mechanism of SNAI3-AS1 in ferroptosis susceptibility of glioma.ResultsWe found that ferroptosis inducer erastin downregulates SNAI3-AS1 expression in glioma by increasing the DNA methylation level of SNAI3-AS1 promoter. SNAI3-AS1 functions as a tumor suppressor in glioma. Importantly, SNAI3-AS1 enhances the anti-tumor activity of erastin by promoting ferroptosis both in vitro and in vivo. Mechanistically, SNAI3-AS1 competitively binds to SND1 and perturbs the m6A-dependent recognition of Nrf2 mRNA 3’UTR by SND1, thereby reducing the mRNA stability of Nrf2. Rescue experiments confirmed that SND1 overexpression and silence can rescue the gain- and loss-of-function ferroptotic phenotypes of SNAI3-AS1, respectively.ConclusionsOur findings elucidate the effect and detailed mechanism of SNAI3-AS1/SND1/Nrf2 signalling axis in ferroptosis, and provide a theoretical support for inducing ferroptosis to improve glioma treatment.

Emerging RNA-Based Therapeutic and Diagnostic Options: Recent Advances and Future Challenges in Genitourinary Cancers

Renal cell carcinoma, bladder cancer, and prostate cancer are the most widespread genitourinary tumors. Their treatment and diagnosis have significantly evolved over recent years, due to an increasing understanding of oncogenic factors and the molecular mechanisms involved. Using sophisticated genome sequencing technologies, the non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have all been implicated in the occurrence and progression of genitourinary cancers. Interestingly, DNA, protein, and RNA interactions with lncRNAs and other biological macromolecules drive some of these cancer phenotypes. Studies on the molecular mechanisms of lncRNAs have identified new functional markers that could be potentially useful as biomarkers for effective diagnosis and/or as targets for therapeutic intervention. This review focuses on the mechanisms underlying abnormal lncRNA expression in genitourinary tumors and discusses their role in diagnostics, prognosis, and treatment.

Characterization of the lncRNA-miRNA-mRNA regulatory network to reveal potential functional competing endogenous RNAs in traumatic brain injury.

Traumatic brain injury (TBI) is one of the most common acute central nervous system injury diseases. Given the medical and socio-economic burdens of TBI patients, the pathogenesis in TBI and the latent intervention targets needed to be further illuminated. Long non-coding RNAs (lncRNAs) had been revealed to play a vital role in the regulation of pathogenesis after TBI. However, the mutual communication and adjustment of lncRNA associated competing for endogenous RNA (ceRNA) networks in TBI have not been explored to date. In this study, we systematically sequenced the whole transcriptome of lncRNAs, miRNAs, and mRNAs between sham and TBI groups and a total of 939 differentially expressed (DE) lncRNAs, 46 DE miRNAs, and 1,951 DE mRNAs were obtained. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein interaction relationship analyses were conducted for DE mRNAs to identify hub DE genes in TBI. Based on the criteria of bioinformatics prediction, the lncRNA associated ceRNA network covering 201 lncRNAs, 22 miRNAs, and 79 mRNAs was constructed. This study provides a novel perspective on the molecular mechanism of lncRNA in TBI and identifies certain lncRNAs as potential therapeutic targets against TBI.

Oviduct Transcriptomic Reveals the Regulation of mRNAs and lncRNAs Related to Goat Prolificacy in the Luteal Phase.

Simple SummaryThe kidding number is an important reproductive trait in domestic goats. The oviduct, as one of the most major organs, is directly involved in the reproductive process, providing nutrition and a location for early embryonic development. The current study provides genome-wide expression profiles of mRNA and long noncoding RNAs (lncRNAs) expression in Yunshang black goat, a new breed of meat goat bred in China with a high kidding number. During the luteal phases, oviduct mRNAs and lncRNAs associated with high- and low-fecundity Yunshang black goats were identified, and their potential biological functions were predicted using GO, KEGG, and GSEA enrichment analysis. These findings shed light on the oviduct-based prolificacy mechanism in goats.The oviduct is associated with embryo development and transportation and regulates the pregnancy success of mammals. Previous studies have indicated a molecular mechanism of lncRNAs in gene regulation and reproduction. However, little is known about the function of lncRNAs in the oviduct in modulating goat kidding numbers. Therefore, we combined RNA sequencing (RNA-seq) to map the expression profiles of the oviduct at the luteal phase from high- and low-fecundity goats. The results showed that 2023 differentially expressed mRNAs (DEGs) and 377 differentially expressed lncRNAs (DELs) transcripts were screened, and 2109 regulated lncRNA-mRNA pairs were identified. Subsequently, the genes related to reproduction (IGF1, FGFRL1, and CREB1) and those associated with embryonic development and maturation (DHX34, LHX6) were identified. KEGG analysis of the DEGs revealed that the GnRH- and prolactin-signaling pathways, progesterone-mediated oocyte maturation, and oocyte meiosis were related to reproduction. GSEA and KEGG analyses of the target genes of DELs demonstrated that several biological processes and pathways might interact with oviduct functions and the prolificacy of goats. Furthermore, the co-expression network analysis showed that XLOC_029185, XLOC_040647, and XLOC_090025 were the cis-regulatory elements of the DEGs MUC1, PPP1R9A, and ALDOB, respectively; these factors might be associated with the success of pregnancy and glucolipid metabolism. In addition, the GATA4, LAMA2, SLC39A5, and S100G were trans-regulated by lncRNAs, predominantly mediating oviductal transport to the embryo and energy metabolism. Our findings could pave the way for a better understanding of the roles of mRNAs and lncRNAs in fecundity-related oviduct function in goats.

RNA sequencing reveals lncRNA-mediated non-mendelian inheritance of feather growth change in chickens

BackgroundLong non-coding RNAs (lncRNAs) play an essential role in biological processes. However, the expression patterns of lncRNAs that regulate the non-Mendelian inheritance feather phenotypes remain unknown.ObjectiveThis study aimed to compare the expression profiles of lncRNAs in the follicles of the late-feathering cocks (LC) and late-feathering hens (LH) that followed genetic rules and the early-feathering hen (EH) and early-feathering cock (EC) that did not conform to the genetic laws.MethodsWe performed RNA sequencing and investigated the differentially expressed lncRNAs (DElncRNAs) between the early- and late-feathering chickens, which function by cis-acting or participate in the competing endogenous RNA (ceRNA) network.ResultsA total of 53 upregulated and 43 downregulated lncRNAs were identified in EC vs. LC, and 58 upregulated and 109 downregulated lncRNAs were identified in EH vs. LH. The target mRNAs regulated by lncRNAs in cis were enriched in the pentose phosphate pathway, TGF-β signaling pathway and Jak-STAT signaling pathway in EC vs. LC and were associated with the TGF-β signaling pathway, Wnt signaling pathway, p53 signaling pathway and Jak-STAT signaling pathway in EH vs. LH. In addition, the lncRNA-mediated ceRNA regulatory pathways of hair follicle formation were mainly enriched in the TGF-β signaling pathway, Wnt signaling pathway, melanogenesis, and calcium signaling pathways. The levels of ENSGALG00000047626 were significantly higher in the late-feathering chickens than in the early-feathering chickens, which regulated the expression of SSTR2 by gga-miR-1649-5p.ConclusionThis study provides a novel molecular mechanism of lncRNA’s response to the feather rate that does not conform to the genetic laws in chickens.

Differential regulation of mRNAs and lncRNAs related to lipid metabolism in Duolang and Small Tail Han sheep

The function of long non-coding RNA (lncRNA) can be achieved through the regulation of target genes, and the deposition of fat is regulated by lncRNA. Fat has an important effect on meat quality. However, there are relatively few studies on lncRNAs in the subcutaneous adipose tissue of Duolang sheep and Small Tail Han sheep. In this study, RNA-Seq technology and bioinformatics methods were used to identify and analyze the lncRNA and mRNA in the subcutaneous adipose tissue of the two breeds of sheep. The results showed that 107 lnRNAs and 1329 mRNAs were differentially expressed. The differentially expressed genes and lncRNA target genes were significantly enriched in the biosynthesis of unsaturated fatty acids signaling pathway, fatty acid metabolism, adipocyte differentiation and other processes related to fat deposition. Among them, LOC105616076, LOC114118103, LOC105607837, LOC101116622, and LOC105603235 target FADS1, SCD, ELOVL6, HSD17B12 and HACD2, respectively. They play a key regulatory role in the biosynthesis of unsaturated fatty acids. This study lays a foundation for the study of the molecular mechanism of lncRNA on fat development, and has reference value for studying the differences in fat deposition between Duolang sheep and Small Tail Han sheep.

High-throughput analysis of lncRNA in cows with naturally infected Staphylococcus aureus mammary gland

LncRNA (long non-coding RNA) is an RNA molecule with a length between 200 and 100,000 nt. It does not encode proteins and is involved in a variety of intracellular processes, becoming a research hotspot of genetics. To identify key lncRNAs associated with dairy mastitis, we collected mammary epithelial tissue samples of Normal disease-free Holstein cows (HCN) and unhealthy Holstein cows with Staphylococcus aureus (HCU) and performed RNA sequencing (RNA-seq) on the samples. A total of 270 differentially expressed lncRNAs and 500 differentially expressed mRNAs were identified by high-throughput sequencing and bioinformatics analysis. Furthermore, Hydrolase activity is the most enriched in GO, and ErbB signaling pathway is significantly enriched in KEGG. In addition, through qPCR validation of 5 candidate lncRNAs in HCN and HCU, four differentially expressed lncRNAs MSTRG.498, MSTRG57.1, MSTRG.41.1 and MSTRG 124.1 were confirmed to have significant differentially expressed in cow mastitis. Also, lncRNA MSTRG.498 and its target gene, SMC4, might directly or indirectly play a role in cow mastitis. The regulatory network of lncRNA-miRNA-mRNA has been inferred from a bioinformatics perspective, which may assist understand the underlying molecular mechanism of lncRNAs involved in regulating mastitis in cows. Our findings will provide meaningful resources for further research on the regulatory function of lncRNAs in cow mastitis.

The Emerging Role of Long Non-Coding RNAs in Esophageal Cancer: Functions in Tumorigenesis and Clinical Implications.

Esophageal cancer (EC) is one of the most common malignancies of digestive tracts with poor five-year survival rate. Hence, it is very significant to further investigate the occurrence and development mechanism of esophageal cancer, find more effective biomarkers and promote early diagnosis and effective treatment. Long non-coding RNAs (lncRNAs) are generally defined as non-protein-coding RNAs with more than 200 nucleotides in length. Existing researches have shown that lncRNAs could act as sponges, guides, scaffolds, and signal molecules to influence the oncogene or tumor suppressor expressions at transcriptional, post-transcriptional, and protein levels in crucial cellular processes. Currently, the dysregulated lncRNAs are reported to involve in the pathogenesis and progression of EC. Importantly, targeting EC-related lncRNAs through genome editing, RNA interference and molecule drugs may be one of the most potential therapeutic methods for the future EC treatment. In this review, we summarized the biological functions and molecular mechanisms of lncRNAs, including oncogenic lncRNAs and tumor suppressor lncRNAs in EC. In addition, we generalized the excellent potential lncRNA candidates for diagnosis, prognosis and therapy in EC. Finally, we discussed the current challenges and opportunities of lncRNAs for EC.

Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use

Deep whole genome and transcriptome sequencing have highlighted the importance of an emerging class of non-coding RNA longer than 200 nucleotides (i.e., long non-coding RNAs (lncRNAs)) that are involved in multiple cellular processes such as cell differentiation, embryonic development, and tissue homeostasis. Cancer is a prime example derived from a loss of homeostasis, primarily caused by genetic alterations both in the genomic and epigenetic landscape, which results in deregulation of the gene networks. Deregulation of the expression of many lncRNAs in samples, tissues or patients has been pointed out as a molecular regulator in carcinogenesis, with them acting as oncogenes or tumor suppressor genes. Herein, we summarize the distinct molecular regulatory mechanisms described in literature in which lncRNAs modulate carcinogenesis, emphasizing epigenetic and genetic alterations in particular. Furthermore, we also reviewed the current strategies used to block lncRNA oncogenic functions and their usefulness as potential therapeutic targets in several carcinomas.

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.

The LINC00152/miR-138 Axis Facilitates Gastric Cancer Progression by Mediating SIRT2.

Gastric cancer (GC) is the most common gastrointestinal cancer and the main cause of tumor-related death. Exploring markers for early diagnosis and new therapeutic targets is always on the way. In the last 10 years, long noncoding RNAs (lncRNAs) have been widely proved to be involved in the progress of many tumors and are regarded as potential targets for tumor therapy. We found that LINC00152, a newly identified lncRNA, was significantly upregulated in GC tissues and affected clinicopathological characteristics in GC patients. Furthermore, we observed that LINC00152 knockdown can significantly reduce cell proliferation and promote apoptosis in human gastric cancer cells. Further bioinformatic analysis indicated that LINC00152 competitively bound with miR-138 and regulated the expression of miR-138. Moreover, SIRT2 was further proved to be a downstream target of miR-138. Overall, this study elucidates the molecular mechanism of LINC00152 underlying the malignant phenotype of GC cells by mediating miR-138/SIRT2 axis, which provides a new understanding of the role and molecular mechanism of lncRNA in GC and also provides a new way for the treatment of gastric cancer.

Role of Long Non-coding RNAs on Bladder Cancer

Bladder cancer (BC) is the most common malignant tumor in the urinary system, and its early diagnosis is conducive to improving clinical prognosis and prolonging overall survival time. However, few biomarkers with high sensitivity and specificity are used as diagnostic markers for BC. Multiple long non-coding RNAs (lncRNAs) are abnormally expressed in BC, and play key roles in tumorigenesis, progression and prognosis of BC. In this review, we summarize the expression, function, molecular mechanisms and the clinical significance of lncRNAs on bladder cancer. There are more than 100 dysregulated lncRNAs in BC, which are involved in the regulation of proliferation, cell cycle, apoptosis, migration, invasion, metabolism and drug resistance of BC. Meanwhile, the molecular mechanisms of lncRNAs in BC was explored, including lncRNAs interacting with DNA, RNA and proteins. Additionally, the abnormal expression of thirty-six lncRNAs is closely associated with multiple clinical characteristics of BC, including tumor size, metastasis, invasion, and drug sensitivity or resistance of BC. Furthermore, we summarize some potential diagnostic and prognostic biomarkers of lncRNA for BC. This review provides promising novel biomarkers in early diagnosis, prognosis and monitoring of BC based on lncRNAs.

Exploring the Potential Key IncRNAs with Endometriosis by Construction of a ceRNA Network.

PurposeThe etiology and pathophysiology of endometriosis remain unclear. Current research indicates long noncoding RNA (lncRNA) may play an important role in the pathogenesis and development of endometriosis. However, the molecular mechanism of lncRNA in endometriosis is far from clear.Patients and MethodsThe lncRNA and mRNA expression of 8 patients with ovarian endometriosis were determined by high-throughput RNA sequencing (8 ectopic endometria samples vs 8 eutopic endometria samples), and miRNA expression profiles were obtained from our previous study. Then a lncRNA-associated competing endogenous RNA (ceRNA) network was constructed by combining the regulatory interaction and negative co-expression interaction between the differentially expressed lncRNAs/mRNAs and miRNAs by different rules.ResultsThe constructed lncRNA-related ceRNA network was composed of two separate networks, network 1 including 14,137 dysregulated lncRNA–mRNA interactions, referring to 242 lncRNAs, 55 miRNAs and 1600 mRNAs, network 2 including 4459 dysregulated lncRNA–mRNA interactions, referring to 111 lncRNAs, 39 miRNAs and 1151 mRNAs. The top six hub lncRNAs (LINC01140, MSC-AS1, HAGLR, CKMT2-AS1, JAKMIP2-AS1, AL365361.1) in the significant ternary relationship of mRNA–miRNA–lncRNA in network 1, and the top six hub lncRNAs (PAX8-AS1, MIR17HC, PART1, HOXA-AS3, PLAC4, LINC00511) in the significant ternary relationship of mRNA–miRNA–lncRNA in network 2 were selected. Functional enrichment analysis of these lncRNA-related mRNAs indicated that the lncRNAs in network 1 mainly take part in positive regulation of phagocytosis, myeloid leukocyte activation, and tissue remodeling, while the lncRNAs in network 2 mainly take part in negative regulation of cell proliferation, blood vessel development and regulation of epithelial cell differentiation, which is consistent with the results obtained from the different rules to construct the networks.ConclusionlncRNA-related ceRNA network analysis recognized key lncRNAs related to the development of endometriosis.

NF-\u03baB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay

Previous study demonstrated that most long non-coding RNAs (lncRNAs) function as competing endogenous RNAs or molecular sponges to negatively modulate miRNA and regulate tumor development. However, the molecular mechanisms of lncRNAs in cancer are not fully understood. Our study describes the role of the lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) in cancer metastasis by mechanisms related to Staufen1 (STAU1)-mediated mRNA decay (SMD). Briefly, we found that, high SPRY4-IT1 expression was associated with aggressiveness and poor outcome in human colorectal, breast and ovarian cancer tissues. In addition, functional assays revealed that SPRY4-IT1 significantly promoted colorectal, breast and ovarian cancer metastasis in vitro and in vivo. Mechanistically, microarray analyses identified several differentially-expressed genes upon SPRY4-IT1 overexpression in HCT 116 colorectal cancer cells. Among them, the 3′-UTR of transcription elongation factor B subunit 1 (TCEB1) mRNA can base-pair with the Alu element in the 3′-UTR of SPRY4-IT1. Moreover, SPRY4-IT1 was found to bind STAU1, promote STAU1 recruitment to the 3′-UTR of TCEB1 mRNA, and affect TCEB1 mRNA stability and expression, resulting in hypoxia-inducible factor 1α (HIF-1α) upregulation, and thereby affecting cancer cell metastasis. In addition, STAU1 depletion abrogated TCEB1 SMD and alleviated the pro-metastatic effect of SPRY4-IT1 overexpression. Significantly, we revealed that SPRY4-IT1 is also transactivated by NF-κB/p65, which activates SPRY4-IT1 to inhibit TCEB1 expression, and subsequently upregulate HIF-1α. In conclusion, our results highlight a novel mechanism of cytoplasmic lncRNA SPRY4-IT1 in which SPRY4-IT1 affecting TCEB1 mRNA stability via STAU1-mediated degradation during cancer metastasis.

Differential expression of long non-coding RNA Regulator of reprogramming and its molecular mechanisms in polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disease in women of reproductive age. Multiple studies have shown that long non-coding RNAs (lncRNA) and microRNAs (miRNA) play a role in PCOS. This study aimed to explore the role and molecular mechanism of lncRNA -Regulator of reprogramming (lncROR) in PCOS.ResultsExpression level of lncROR in PCOS patients was up-regulated, while level of miR-206 was down-regulated in comparison with control group (P < 0.001). Logistics regression analysis showed that lncROR and miR-206 were independent predictors of PCOS. The ROC curve showed that lncROR had a high diagnostic value for PCOS with an AUC value of 0.893. Pearson correlation coefficient indicated that the expression level of miR-206 was negatively correlated with the level of lncROR. CCK-8 assay and apoptosis assay revealed that downregulation of lncROR up-regulated the expression of miR-206, thereby inhibiting cell proliferation and promoting cell apoptosis. However, silencing the expression of miR-206 reversed the above effects caused by down-regulation of lncROR expression. Luciferase reporter gene assay suggested that there was a target relationship between lncROR and miR-206. VEGF was proved to be the target gene of miR-206.ConclusionsHighly expressed lncROR indirectly up-regulated the expression of VEGF by down-regulating the expression of miR-206, thereby promoting the proliferation of KGN cells and inhibiting apoptosis, and further promoting the development of PCOS.

Pathological Bases and Clinical Application of Long Noncoding RNAs in Cardiovascular Diseases.

Increasing evidence has suggested that noncoding RNAs (ncRNAs) have vital roles in cardiovascular tissue homeostasis and diseases. As a main subgroup of ncRNAs, long ncRNAs (lncRNAs) have been reported to play important roles in lipid metabolism, inflammation, vascular injury, and angiogenesis. They have also been implicated in many human diseases including atherosclerosis, arterial remodeling, hypertension, myocardial injury, cardiac remodeling, and heart failure. Importantly, it was reported that lncRNAs were dysregulated in the development and progression of cardiovascular diseases (CVDs). A variety of studies have demonstrated that lncRNAs could influence gene expression at transcription, post-transcription, translation, and post-translation level. Particularly, emerging evidence has confirmed that the crosstalk among lncRNAs, mRNA, and miRNAs is an important underlying regulatory mechanism of lncRNAs. Nevertheless, the biological functions and molecular mechanisms of lncRNAs in CVDs have not been fully explored yet. In this review, we will comprehensively summarize the main findings about lncRNAs and CVDs, highlighting the most recent discoveries in the field of lncRNAs and their pathophysiological functions in CVDs, with the aim of dissecting the intrinsic association between lncRNAs and common risk factors of CVDs including hypertension, high glucose, and high fat. Finally, the potential of lncRNAs functioning as the biomarkers, therapeutic targets, as well as specific diagnostic and prognostic indicators of CVDs will be discussed in this review.

LncRNA SGMS1-AS1 regulates lung adenocarcinoma cell proliferation, migration, invasion, and EMT progression via miR-106a-5p/MYLI9 axis.

BackgroundLung cancer mainly includes non‐small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the main subtype of NSCLC. Long non‐coding RNAs (LncRNAs) had been found to exert numerous functions on the progressions of cancers. MicroRNAs often exist as the target of LncRNAs to regulate a series of signaling pathways in human. We explored the effects and molecular mechanism of LncRNA SGMS1‐AS1 on the procedures of LUAD cells.MethodsThe ENCORI and GEPIA databases were used to analyze the differences in SGMS1, miR‐106a‐5p, and MYLIP between LUAD and normal tissue. Their expression levels were examined by RT‐PCR. CCK8, colony formation, migration, and invasion assay were conducted in LUAD cells which had silenced SGMS1‐AS1. To verify the relationship between SGMS1‐AS1, miR‐106a‐5p, and MYLIP, we overexpressed miR‐106a‐5p inhibitor or MYLIP in LUAD cells after decreasing SGMS1‐AS1 and repeated the above assays.ResultsSGMS1‐AS1 was downregulated in LUAD tissue as well as cells, which was related to good prognosis of patients with lung adenocarcinoma. Additionally, knockdown of SGMS1‐AS1 promoted proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression of LUAD cells, which meant that SGMS1‐AS1 inhibited the progression of LUAD cells. Furthermore, miR‐106a‐5p was the direct target of SGMS1‐AS1 and transfecting miR‐106a‐5p inhibitor could reversed the impact induced by knockdown of SGMS1‐AS1. Subsequently, we found that MYLIP was the target of miR‐106a‐5p, which was negatively correlated with miR‐106a‐5p, but had high positive correlation with SGMS1‐AS1. Consistently, overexpression MYLIP partly eliminated the effects on A549 cells induced by silencing of SGMS1‐AS1.ConclusionLncRNA SGMS1‐AS1 inhibits the proliferation, invasion, migration and EMT progression of LUAD cells via targeting miR‐106a‐5p/MYLIP axis.

Integrated Analysis of Long Noncoding RNA Expression Profiles in Acute-on-Chronic Liver Failure.

People infected with chronic hepatitis B virus (HBV) might progress to acute-on-chronic liver failure (ACLF) with a high fatality rate. Long noncoding RNAs (lncRNAs) are involved in human diseases, but it is unknown whether lncRNAs are involved in the progression of chronic HBV infection to ACLF. Hence, this study is aimed at systemically identifying and characterizing the landscape and the molecular mechanism of lncRNAs in the pathogenesis of chronic HBV infection progress to ACLF. RNA sequencing (RNA-Seq) of peripheral blood samples from 5 ACLF and 5 HBV infection patients was performed. We detected 9733 lncRNAs, including 406 annotated lncRNAs and 9327 novel lncRNAs. A total of 407 lncRNAs were found to be significantly dysregulated in the patients with ACLF as compared with those in the chronic HBV infection patients. The flanking protein-coding genes of differentially expressed lncRNAs were enriched with pathways that might contribute to the pathogenesis of ACLF, such as the WNT signaling pathway. Furthermore, 9 selected differentially expressed lncRNAs validated by the qRT-PCR, showing that the expression patterns of these 9 lncRNAs were consistent with the RNA-Seq data. Four selected differentially expressed lncRNAs were also validated in another patient cohort comprising 80 patients with ACLF and 65 patients with chronic HBV infection. Aberrant lncRNAs might be used to develop novel diagnostic biomarkers or drug targets for ACLF.