Functions Of lncRNAs Research Articles

Rules and impacts of nonsense-mediated mRNA decay in the degradation of long noncoding RNAs.

Nonsense-mediated mRNA decay (NMD) is a quality-control process that selectively degrades mRNAs having premature termination codon, upstream open reading frame, or unusually long 3'UTR. NMD detects such mRNAs and rapidly degrades them during initial rounds of translation in the eukaryotic cells. Since NMD is a translation-dependent cytoplasmic mRNA surveillance process, the noncoding RNAs were initially believed to be NMD-resistant. The sequence feature-based analysis has revealed that many putative long noncoding RNAs (lncRNAs) have short open reading frames, most of which have translation potential. Subsequent transcriptome-based molecular studies showed an association of a large set of such putative lncRNAs with translating ribosomes, and some of them produce stable and functionally active micropeptides. The translationally active lncRNAs typically have relatively longer and unprotected 3'UTR, which can induce their NMD-dependent degradation. This review defines the mechanism and regulation of NMD-dependent degradation of lncRNAs and its impact on biological processes related to the functions of lncRNAs or their encoded micropeptides. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease.

The roles of long non-coding RNAs in ovarian cancer: from functions to therapeutic implications.

Long non-coding RNAs (lncRNAs) are multifunctional and participate in a variety of biological processes and gene regulatory networks. The deregulation of lncRNAs has been extensively implicated in diverse human diseases, especially in cancers. Overwhelming evidence demonstrates that lncRNAs are essential to the pathophysiological processes of ovarian cancer (OC), acting as regulators involved in metastasis, cell death, chemoresistance, and tumor immunity. In this review, we illustrate the expanded functions of lncRNAs in the initiation and progression of OC and elaborate on the signaling pathways in which they pitch. Additionally, the potential clinical applications of lncRNAs as biomarkers in the diagnosis and treatment of OC were emphasized, cementing the bridge of communication between clinical practice and basic research.

Involvement of lncRNAs in the regulation of aerobic glycolysis in hepatocellular carcinoma: Main functions, regulatory mechanisms and potential therapeutic implications (Review).

Even under aerobic conditions, tumor cells can reprogram their metabolism to preferentially metabolize glucose into lactic acid. This abnormal metabolic pattern, known as the 'Warburg' effect or aerobic glycolysis, promotes cancer progression. Long non‑coding RNAs (lncRNAs) are RNAs that are >200 nucleotides in length and do not have protein‑coding capabilities. However, these RNAs play a key role in tumor development. There is increasing evidence to indicate that lncRNAs regulate glucose metabolism in tumor cells by affecting metabolic enzymes and some signaling pathways, thereby regulating the occurrence and progression of hepatocellular carcinoma (HCC). Therefore, it is crucial to understand which lncRNAs play a regulatory role in HCC glycolysis and to determine the related molecular mechanisms. The present review summarized and discussed the functions of lncRNAs, focusing on the regulatory mechanisms of lncRNAs in the process of glycolysis in HCC. In addition, the present review suggests the importance of lncRNAs as future therapeutic targets for antitumor cell metabolism.

LncRNA RP11-301G19.1 is required for the maintenance of vascular smooth muscle cell contractile phenotype via sponging miR-17-5P/ATOH8 axis.

Long noncoding RNAs (LncRNAs) play essential roles in regulating gene expression in various biological processes. However, the function of lncRNAs in vascular smooth muscle cell (VSMC) transformation remains to be explained. In this work, we discover that a new bone marrow protein (BMP) signaling target, lncRNA RP11-301G19.1, is significantly induced in BMP7-treated VSMCs through lncRNA microarray analysis. Addition of BMP signaling inhibitor LDN-193189 attenuates the expression of ACTA2 and SM-22α, as well as the mRNA level of RP11-301G19.1. Furthermore, lncRNA RP11-301G19.1 is critical to the VSMC differentiation and is directly activated by SMAD1/9. Mechanistically, knocking down of RP11-301G19.1 leads to the decrease of ATOH8, another BMP target, while the forced expression of RP11-301G19.1 reactivates ATOH8. In addition, miR-17-5p, a miRNA negatively regulated by BMP-7, contains predicted binding sites for lncRNA RP11-301G19.1 and ATOH8 3'UTR. Accordingly, overexpression of miR-17-5p decreases the levels of them. Together, our results revealed the role of lncRNA RP11-301G19.1 as a miRNA sponge to upregulate ATOH8 in VSMC phenotype transformation.

Cell Type- and Age-Specific Expression of lncRNAs across Kidney Cell Types.

Accumulated evidence demonstrates that long non-coding RNAs (lncRNAs) regulate cell differentiation and homeostasis, influencing kidney aging and disease. Despite their versatility, the function of lncRNA remains poorly understood due to the lack of a reference map of lncRNA transcriptome in various cell types. In this study, we employed a targeted single-cell RNA sequencing (scRNA-seq) method to enrich and characterize lncRNAs in individual cells. We applied this method to various mouse tissues, including normal and aged kidneys. Through tissue-specific clustering analysis, we identified cell type-specific lncRNAs that showed a high correlation with known cell-type marker genes. Furthermore, we constructed gene regulatory networks (GRNs) to explore the functional roles of differentially expressed lncRNAs in each cell type. In the kidney, we observed dynamic expression changes of lncRNAs during aging, with specific changes in glomerular cells. These cell type- and age-specific expression patterns of lncRNAs provide insights into their potential roles in regulating cellular processes, such as immune response and energy metabolism, during kidney aging. Our study sheds light on the comprehensive landscape of lncRNA expression and function and provides a valuable resource for future analysis of lncRNAs (https://gist-fgl.github.io/sc-lncrna-atlas/).

Discovery of long non-coding RNAs in naïve CD4+ T cells in response to initiating antiretroviral therapy at acute or chronic phase of HIV-1 infection

Long non-coding RNAs (lncRNAs) have gained prominence due to their involvement in various cellular processes, but their specific roles remain elusive. Dysregulation of lncRNAs has been implicated in the pathogenesis of several diseases. In this study, we aimed to shed light on the role of lncRNAs in individuals infected with human immunodeficiency virus type 1 (HIV-1) by examining their changes in the expression patterns related to the initiation of antiretroviral therapy (ART) during acute or chronic phases of infection, compared to healthy controls. We found 316 differentially expressed (DE) lncRNAs in patients receiving long-term ART, shedding light on their potential roles. We also observed interactions between these DE lncRNAs and specific microRNAs (miRNAs). Some of these miRNAs, such as hsa-miR-574-5p, hsa-miR-765, hsa-miR-6165, hsa-miR-1207-5p, and hsa-miR-378i, are associated with cancer progression or suppression, while others, including hsa-miR-328-5p, hsa-miR-4753-3p, and MiR-664, play roles in immune system regulation. Furthermore, our study revealed substantial enrichment in distinct Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as axon guidance, PI3K-Akt signaling, and MAPK signaling pathways. Although our results indicate possible molecular processes impacted by the discovered lncRNAs, we cannot explicitly establish causality or specific connections between lncRNAs and genes in these pathways, fostering more specific studies. Furthermore, Gene Ontology (GO) analysis highlighted terms such as cytoskeletal protein binding, ion channel function, synaptic processes, neuron projection, and the somatodendritic compartment, underscoring the relevance of lncRNAs in these cellular components within the context of HIV-1 infection and ART treatment. In conclusion, our study emphasizes the need for further exploration of lncRNAs as potential biomarkers and therapeutic targets in HIV-1-infected patients, with a particular focus on CD4+ T cells. Understanding the functions of lncRNAs in these contexts may pave the way for novel treatment strategies and improved patient outcomes, aligning with the broader goals of our research.

Macrophage-enriched novel functional long noncoding RNAs LRRC75A-AS1 and GAPLINC regulate polarization and innate immune responses.

Macrophages (Mφs) are functionally dynamic immune cells that bridge innate and adaptive immune responses; however, the underlying epigenetic mechanisms that control Mφ plasticity and innate immune functions are not well elucidated. To identify novel functions of macrophage-enriched lncRNAs in regulating polarization and innate immune responses. Total RNA isolated from differentiating monocyte-derived M1 and M2 Mφs was profiled for lncRNAs expression using RNAseq. Impact of LRRC75A-AS1, GAPLINC and AL139099.5 knockdown was examined on macrophage differentiation,polarization markers, phagocytosis, and antigen processing by flow cytometry and florescence microscopy. Cytokine profiles were examined by multiplex bead array and cytoskeletal signaling pathway genes were quantified by PCR-based array. Gingival biopsies were collected from periodontally healthy and diseased subjects to examine lncRNAs,M1/M2marker expression. Transcriptome profiling of M1 and M2 Mφs identified thousands of differentially expressed known and novel lncRNAs. We characterized three Mφ-enriched lncRNAs LRRC75A-AS1, GAPLINC and AL139099.5 in polarization and innate immunity. Knockdown of LRRC75A-AS1 and GAPLINC downregulated the Mφ differentiation markers and skewed Mφ polarization by decreasing M1 markers without a significant impact on M2 markers. LRRC75A-AS1 and GAPLINC knockdown also attenuated bacterial phagocytosis, antigen processing and inflammatory cytokine secretion in Mφs, supporting their functional role in potentiating innate immune functions. Mechanistically, LRRC75A-AS1 and GAPLINC knockdown impaired Mφ migration by downregulating the expression of multiple cytoskeletal signaling pathways suggesting their critical role in regulating Mφ migration. Finally, we showed that LRRC75A-AS1 and GAPLINC were upregulated in periodontitis and their expression correlates with higher M1 markers suggesting their role in macrophage polarizationin vivo. Our results show that polarized Mφs acquire a unique lncRNA repertoire and identified many previously unknown lncRNA sequences. LRRC75A-AS1 and GAPLINC, which are induced in periodontitis, regulate Mφ polarization and innate immune functions supporting their critical role in inflammation.

Identification and verification of a PANoptosis-related long noncoding ribonucleic acid signature for predicting the clinical outcomes and immune landscape in lung adenocarcinoma

PANoptosis is a type of programmed cell death (PCD) characterised by apoptosis, necroptosis and pyroptosis. Long non-coding ribonucleic acids (lncRNAs) are participating in the malignant behaviour of tumours regulated by PCD. Nevertheless, the function of PANoptosis-associated lncRNAs in lung adenocarcinoma remains to be investigated. In this work, a PANoptosis-related lncRNA signature (PRLSig) was developed based on the least absolute shrinkage and selection operator algorithm. The stability and fitness of PRLSig were confirmed by systematic evaluation of Kaplan–Meier, Cox analysis algorithm, receiver operating characteristic analysis, stratification analysis. In addition, ESTIMATE, single sample gene set enrichment analysis, immune checkpoints and the cancer immunome database confirmed the predictive value of the PRLSig in immune microenvironment and helped to identify populations for which immunotherapy is advantageous. The present research provides novel insights to facilitate risk stratification and optimise personalised treatment for LUAD.

Potential role of lncRNA LOXL1-AS1 in human cancer development: a narrative review.

Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs consisting of more than 200 nucleotides that are widely involved in various physiological and pathobiological processes in the body. LncRNA plays a crucial role in tumorigenesis and development with its unique functions, such as playing a role in a variety of biological processes of malignant tumors as a cancer-promoting factor or a cancer-suppressor factor. Lysyl oxidase-like protein 1-antisense RNA1 (LOXL1-AS1) is a novel functional lncRNA recently reported. This article reviews the current findings on the role of LOXL1-AS1 in cancer, and discusses the potential clinical significance and application prospects, in order to provide a theoretical basis and reference for the clinical diagnosis, treatment and screening of prognostic markers for malignant tumors. The PubMed and Embase databases were searched using the keywords "cancer" or "tumor" or "neoplasm" and "LOXL1-AS1" for publications from 2018 to the present. The English literature was searched, with a focus on relevant articles. These articles validated the role and mechanism of LOXL1-AS1 in different cancers. LOXL1-AS1 is a recently reported novel lncRNA, which is abnormally expressed and upregulated in more than ten cancers, and is positively correlated with adverse clinical features and poor prognosis in cancer patients. LOXL1-AS1 competently binds to a variety of microRNAs to regulate the expression of downstream target genes and regulate related signaling pathways, including proliferation, migration, invasion and inhibition of malignant biological behaviors such as apoptosis. LOXL1-AS1 is expected to become a novel biomarker for cancer diagnosis and treatment, with great potential as an independent prognostic indicator.

Knockdown of lncRNA AU020206 could inhibit microglia apoptosis in ischemic stroke.

The diagnostic biomarkers associated with ischemic stroke (IS) that may have clinical utility remain elucidated. Thus, the potential functional lncRNAs in IS were explored. The Gene Expression Omnibus database provided the transcriptome profile of IS for download. WGCNA analysis and integrated bioinformatics were used to find genes that were differentially expressed (DEGs). The Starbase database created the lncRNA-based ceRNA network. In order to investigate the molecular mechanism and involved pathways of DEGs in IS, functional enrichment analysis was carried out. Using qRT-PCR, lncRNAs identified as putative IS biomarkers were confirmed to be expressed in a permanent middle cerebral artery occlusion (MCAO) model. Using the annexin V/PI apoptosis test, the amount of apoptosis in oxygen-glucose deprivation (OGD) cells was measured. A total of 1600 common differentially expressed - protein-coding RNA (DE-pcRNAs) and 26 DE-lncRNAs were identified. The results of enrichment analysis indicate that the cytokine may be regulated by common DE-pcRNAs and are vital in the progress of IS. A lncRNAs-mediated ceRNA network including lncRNAs AU020206, Brip1os, F630028O10Rik and 9530082P21Rik was constructed. The expression of these lncRNAs was significantly increased in MCAO model. Knockdown of lncRNA AU020206 inhibited microglia apoptosis in OGD cell model. We constructed a lncRNAs-mediated ceRNA network and found that lncRNA AU020206 inhibited microglia apoptosis in OGD cell model. These findings provided further evidence for the diagnosis and a novel avenue for targeted therapy of IS.

Unboxing the network among long non-coding RNAs and TGF-β signaling in cancer.

Deeper analysis of molecular mechanisms arising in tumor cells is an unmet need to provide new diagnostic and therapeutic strategies to prevent and treat tumors. The transforming growth factor β (TGF-β) signaling has been steadily featured in tumor biology and linked to poor prognosis of cancer patients. One pro-tumorigenic mechanism induced by TGF-β is the epithelial-to-mesenchymal transition (EMT), which can initiate cancer dissemination, enrich the tumor stem cell population, and increase chemoresistance. TGF-β signals via SMAD proteins, ubiquitin ligases, and protein kinases and modulates the expression of protein-coding and non-coding RNA genes, including those encoding larger than 500 nt transcripts, defined as long non-coding RNAs (lncRNAs). Several reports have shown lncRNAs regulating malignant phenotypes by directly affecting epigenetic processes, transcription, and post-transcriptional regulation. Thus, this review aims to update and summarize the impact of TGF-β signaling on the expression of lncRNAs and the function of such lncRNAs as regulators of TGF-β signaling, and how these networks might impact specific hallmarks of cancer.

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.

Abstract 5683: lncRNA-protein interactions that predict response to endocrine therapy in HR+ breast cancer

Abstract Hormone receptor positive (HR+) breast cancer (BCa) is the most frequently diagnosed BCa type accounting for 70% of all breast cancer cases. A large population of HR+ BCa patients (30-40%) are resistant to mainstay endocrine therapy and develop incurable metastatic disease. Hence, it is imperative to identify viable biomarkers that stratify patients as drug responders or non-responders. Emerging scientific literature highlights the essential role of long non-coding RNAs (lncRNA) in cancer drug resistance and metastatic transformation; lncRNA include RNAs over 200 nucleotides in length that do not encode protein. Major biological functions of lncRNA rely on association with select protein interactors. As lncRNA equally bind proteins with and without canonical RNA-binding motifs, it is unclear what facilitates this lncRNA-protein interaction. Our recent studies show that SUMO post-translational modification (or SUMOylation) of target proteins potentiates binding with lncRNA, particularly at the chromatin. Using a small-scale screening, we see that SUMO-modification works to enhance association with lncRNAs for proteins with and without a canonical RNA binding domain (RBD). SUMOylation of RBD-expressing heterochromatin protein 1 α (HP1α) drives interaction with multiple chromatin-associated lncRNA both within and outside canonical heterochromatin foci. Interaction with lncRNA supports SUMOylated HP1α’s unconventional function as a transcriptional repressor at select euchromatic loci. We now report an inverse relationship in which SUMOylated HP1α directs the stability of its lncRNA binding partner. Specifically, SUMO-modified HP1α directs cell-cycle dependent recruitment of the RNA degradation machinery to the chromatin and facilitates clearance of chromatin-bound lncRNA. This dynamic lncRNA degradation process is disturbed with cancer onset and instead favors aberrant cancer cell transformation. Consistently, restoring lncRNA degradation homeostasis decreases metastatic properties of HR+ BCa cells and increases sensitivity to targeted therapeutics currently in clinical trials. Our studies define a fundamental mechanism that dictates lncRNA stability and/or degradation in BCa cells. In addition, we present viable biomarkers that predict sensitivity to ET and alternative targeted therapies. Citation Format: Kacie D. Waiters, Maram Quttina, Ashfia F. Khan, Samaneh Karami, Anthony S. Peidl, Funmi Babajide, Tasneem Bawa-Khalfe. lncRNA-protein interactions that predict response to endocrine therapy in HR+ breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5683.

Unveiling the Hidden Regulators: The Impact of lncRNAs on Zoonoses.

Zoonoses are diseases and infections naturally transmitted between humans and vertebrate animals. They form the dominant group of diseases among emerging infectious diseases and represent critical threats to global health security. This dilemma is largely attributed to our insufficient knowledge of the pathogenesis regarding zoonotic spillover. Long non-coding RNAs (lncRNAs) are transcripts with limited coding capacity. Recent technological advancements have enabled the identification of numerous lncRNAs in humans, animals, and even pathogens. An increasing body of literature suggests that lncRNAs function as key regulators in zoonotic infection. They regulate immune-related epigenetic, transcriptional, and post-transcriptional events across a broad range of organisms. In this review, we discuss the recent research progress on the roles of lncRNAs in zoonoses. We address the classification and regulatory mechanisms of lncRNAs in the interaction between host and zoonotic pathogens. Additionally, we explore the surprising function of pathogen-derived lncRNAs in mediating the pathogenicity and life cycle of zoonotic bacteria, viruses, and parasites. Understanding how these lncRNAs influence the zoonotic pathogenesis will provide important therapeutic insights to the prevention and control of zoonoses.

Identification of CAF-related lncRNAs at the pan-cancer level represents a potential carcinogenic risk.

Cancer-associated fibroblasts (CAFs) are increasingly recognized as playing a crucial role in regulating cancer progression and metastasis. These cells can be activated by long non-coding RNAs (lncRNAs), promoting the malignant biological processes of tumor cells. Therefore, it is essential to understand the regulatory relationship between CAFs and lncRNAs in cancers. Here, we identified CAF-related lncRNAs at the pan-cancer level to systematically predict their potential regulatory functions. The identified lncRNAs were also validated using various external data at both tissue and cellular levels. This study has revealed that these CAF-related lncRNAs exhibit expression perturbations in cancers and are highly correlated with the infiltration of stromal cells, particularly fibroblasts and endothelial cells. By prioritizing a list of CAF-related lncRNAs, we can further distinguish patient subtypes that show survival and molecular differences. In addition, we have developed a web server, CAFLnc (https://46906u5t63.zicp.fun/CAFLnc/), to visualize our results. In conclusion, CAF-related lncRNAs hold great potential as a valuable resource for comprehending lncRNA functions and advancing the identification of biomarkers for cancer progression and therapeutic targets in cancer treatment.

The landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses

Long non-coding RNAs (lncRNAs) could modulate expression of immune checkpoints (ICPs) by cooperating with immunity genes in tumor immunization. However, precise functions in immunity and potential for predicting ICP inhibitors (ICI) response have been described for only a few lncRNAs. Here we present an integrated framework that leverages network-based analyses and Bayesian network inference to identify the regulated relationships including lncRNA, ICP and immunity genes as ICP-related LncRNAs mediated Core Regulatory Circuitry Triplets (ICP-LncCRCTs) that can make robust predictions. Hub ICP-related lncRNAs such as MIR155HG and ADAMTS9-AS2 were highlighted to play central roles in immune regulation. Specific ICP-related lncRNAs could distinguish cancer subtypes. Moreover, the ICP-related lncRNAs are likely to significantly correlated with immune cell infiltration, MHC, CYT. Some ICP-LncCRCTs such as CXCL10-MIR155HG-ICOS could better predict one-, three- and five-year prognosis compared to single molecule in melanoma. We also validated that some ICP-LncCRCTs could effectively predict ICI-response using three kinds of machine learning algorithms follow five independent datasets. Specially, combining ICP-LncCRCTs with the tumor mutation burden (TMB) improves the prediction of ICI-treated melanoma patients. Altogether, this study will improve our grasp of lncRNA functions and accelerating discovery of lncRNA-based biomarkers in ICI treatment.

Long noncoding RNA LRG modulates Drosophila locomotion by sequestering Synaptotagmin 1 protein.

Apparently, the genomes of many organisms are pervasively transcribed, and long noncoding RNAs (lncRNAs) make up the majority of cellular transcripts. LncRNAs have been reported to play important roles in many biological processes; however, their effects on locomotion are poorly understood. Here, we presented a novel lncRNA, Locomotion Regulatory Gene (LRG), which participates in locomotion by sequestering Synaptotagmin 1 (SYT1). LRG deficiency resulted in higher locomotion speed which could be rescued by pan-neuronal overexpression but not by limited ellipsoid body, motoneuron or muscle-expression of LRG. At the molecular level, the synaptic vesicles (SVs) release and movement-related SYT1 protein was recognized as LRG-interacting protein candidate. Furthermore, LRG had no effects on SYT1 expression. Genetically, the behavioral defects in LRG mutant could be rescued by pan-neuronal knock-down of Syt1. Taken together, all the results suggested LRG exerts regulatory effects on locomotion via sequestering SYT1 thereby blocking its function without affecting its expression. Our work displays a new function of lncRNA and provides insights for revealing the pathogenesis of neurological diseases with motor disorders.

Analysis of disulfidptosis- and cuproptosis-related LncRNAs in modulating the immune microenvironment and chemosensitivity in colon adenocarcinoma.

The main objective was to establish a prognostic model utilising long non-coding RNAs associated with disulfidptosis and cuproptosis. The data for RNA-Sequence and clinicopathological information of Colon adenocarcinoma (COAD) were acquired from The Cancer Genome Atlas. A prognostic model was constructed using Cox regression and the Least Absolute Shrinkage and Selection Operator method. The model's predictive ability was assessed through principal component analysis, Kaplan-Meier analysis, nomogram etc. The ability of identifying the rates of overall survival, infiltration of immune cells, and chemosensitivity was also explored. In vitro experiments were conducted for the validation of differential expression and function of lncRNAs. A disulfidptosis and cuproptosis-related lncRNA prognostic model was constructed. The prognostic model exhibits excellent independent predictive capability for patient outcomes. Based on the authors' model, the high-risk group exhibited higher tumour mutation burdened worse survival. Besides, differences in immune cell infiltration and responsiveness to chemotherapeutic medications exist among patients with different risk scores. Furthermore, aberrant expressions in certain lncRNAs have been validated in HCT116 cells. In particular, FENDRR and SNHG7 could affect the proliferation and migration of colorectal cancer cells. Our study developed a novel prognostic signature, providing valuable insights into prognosis, immune infiltration, and chemosensitivity in COAD patients.

Integrated Analysis of lncRNAs and mRNAs Reveals Complex Gene Network Mediated by lncRNAs and Regulatory Function of MuLRR-RLK-AS in Response to Phytoplasma Infection in Mulberry.

Phytoplasma disease is one of the most serious infectious diseases that affects the growth and development of mulberry. Long non-coding RNAs (lncRNAs) play an important role in plants' defense systems; however, the contribution of lncRNAs in the response to phytoplasma infection in mulberry is still largely unknown. Herein, strand-specific RNA sequencing was performed to profile the mRNAs and lncRNAs involved in the response to phytoplasma infection in mulberry, and a total of 4169 genes were found to be differentially expressed (DE) between healthy and phytoplasma-infected leaves. Moreover, 1794 lncRNAs were identified, of which 742 lncRNAs were DE between healthy and infected leaves. Target prediction showed that there were 68 and 44 DE lncRNAs which may function as cis and trans-regulators, targeting 54 and 44 DE genes, respectively. These DE target genes are associated with biological processes such as metabolism, signaling, development, transcriptional regulation, etc. In addition, it was found that the expression of the antisense lncRNA (MuLRR-RLK-AS) of the leucine-rich repeat receptor-like protein kinase gene (MuLRR-RLK) was decreased in the phytoplasma-infected leaves. Interestingly, it was found that overexpression of MuLRR-RLK-AS can inhibit the expression of MuLRR-RLK. Moreover, it was found that the expression levels of PTI-related and MAPK genes in the transgenic MuLRR-RLK Arabidopsis plants were significantly higher than those in the wild-type plants when inoculated with pathogens, and the transgenic plants were conferred with strong disease resistance. Our results demonstrate that MuLRR-RLK-AS, as a trans-regulatory factor, can inhibit the expression of the MuLRR-RLK gene and is a negative regulatory factor for mulberry resistance. The information provided is particularly useful for understanding the functions and mechanisms of lncRNAs in the response to phytoplasma infection in mulberry.

LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinoma

Sorafenib resistance is one of the main causes of poor prognosis in patients with advanced hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) function as suppressors or oncogenic factors during tumor progression and drug resistance. Here, to identify therapeutic targets for HCC, the biological mechanisms of abnormally expressed lncRNAs were examined in sorafenib-resistant HCC cells. Specifically, we established sorafenib-resistant HCC cell lines (Huh7-S and SMMC7721-S), which displayed an epithelial-mesenchymal transition (EMT) phenotype. Transcriptome sequencing (RNA-Seq) was performed to established differential lncRNA expression profiles for sorafenib-resistant cells. Through this analysis, we identified LINC00540 as significantly up-regulated in sorafenib-resistant cells and a candidate lncRNA for further mechanistic investigation. Functionally, LINC00540 knockdown promoted sorafenib sensitivity and suppressed migration, invasion, EMT and the activation of PI3K/AKT signaling pathway in sorafenib-resistant HCC cells, whereas overexpression of LINC00540 resulted in the opposite effects in parental cells. LINC00540 functions as a competing endogenous RNA (ceRNA) by competitively binding to miR-4677-3p , thereby promoting AKR1C2 expression. This is the first study that demonstrates a role for LINC00540 in enhancing sorafenib resistance, migration and invasion of HCC cells through the LINC00540/miR-4677-3p/AKR1C2 axis, suggesting that LINC00540 may represent a potential therapeutic target and prognosis biomarker for HCC.