Potential Roles of Long Non-coding RNAs in Regulating Cell Proliferation, Invasion, and Metastasis in Ovarian Serous Cystadenocarcinoma

Abstract Background: Ovarian serous cystadenocarcinoma (OSC) is the most common gynecological malignancy. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and involved in cell proliferation, apoptosis, angiogenesis, and invasion. Here, we investigated the functional roles of lncRNAs in OSC in detail.Methods: We analyzed a cohort of exon microarray datasets from The Cancer Genome Atlas and used differentially expressed lncRNAs and mRNAs to construct an lncRNA-mRNA co-expression network. Distinct lncRNAs were classified into lincRNA, enhancer-like lncRNAs, or antisense lncRNAs. Biological functions for lncRNAs were predicted according to the lncRNA-mRNA network and genomic adjacency by KEGG pathway analysis. A transcription factor (TF)-lncRNA regulatory network was constructed by integrating lncRNA molecular profiles and TF binding information. Results: We identified 2,939 lncRNAs and 2,766 mRNAs that were differentially expressed between OSC and normal ovary tissues. The 67 lncRNAs in the lncRNA-mRNA network, 23 lincRNAs, 19 antisense lncRNAs, and four enhancer-like lncRNAs were involved in cell proliferation, invasion, and metastasis. The TFs ING4, TTF-1, RUSH-l alpha, Kaiso, and STAT1 targeted regulation of lncRNAs in the pathological processes of OSC. Expression of 10 lncRNAs and mRNAs, as well as SOS1, ITGB1, and BIRC2 mRNAs with their identified lncRNAs were verified by qRT-PCR in OSC tissues. Conclusions: We predicted the biological functions of many lncRNAs, which may serve as diagnostic and prognostic biomarkers as well as therapeutic targets in OSC.

Download Full-text

Potential Roles of Long Non-Coding RNAs in Regulating Cell Proliferation, Invasion, and Metastasis in Ovarian Serous Cystadenocarcinoma

10.21203/rs.3.rs-770129/v1 ◽

2021 ◽

Author(s):

Mujie Kan ◽

Housen Zhang ◽

Chengya Dong ◽

Tianmin Xu ◽

Qi Li

Keyword(s):

Cell Proliferation ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Biological Functions ◽

Invasion And Metastasis ◽

Gynecological Malignancy ◽

Functional Roles ◽

Serous Cystadenocarcinoma ◽

Antisense Lncrnas ◽

Non Coding Rnas

Abstract Background: Ovarian serous cystadenocarcinoma (OSC) is the most common gynecological malignancy. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and involved in cell proliferation, apoptosis, angiogenesis, and invasion. Here, we investigated the functional roles of lncRNAs in OSC in detail.Methods: We analyzed a cohort of exon microarray datasets from The Cancer Genome Atlas and used differentially expressed lncRNAs and mRNAs to construct an lncRNA-mRNA co-expression network. Distinct lncRNAs were classified into lincRNA, enhancer-like lncRNAs, or antisense lncRNAs. Biological functions for lncRNAs were predicted according to the lncRNA-mRNA network and genomic adjacency by KEGG pathway analysis. A transcription factor (TF)-lncRNA regulatory network was constructed by integrating lncRNA molecular profiles and TF binding information. Results: We identified 2,939 lncRNAs and 2,766 mRNAs that were differentially expressed between OSC and normal ovary tissues. The 67 lncRNAs in the lncRNA-mRNA network, 23 lincRNAs, 19 antisense lncRNAs, and four enhancer-like lncRNAs were involved in cell proliferation, invasion, and metastasis. The TFs ING4, TTF-1, RUSH-l alpha, Kaiso, and STAT1 targeted regulation of lncRNAs in the pathological processes of OSC. Expression of 10 lncRNAs and mRNAs, as well as SOS1, ITGB1, and BIRC2 mRNAs with their identified lncRNAs were verified by qRT-PCR in OSC tissues. Conclusion: We predicted the biological functions of many lncRNAs, which may serve as diagnostic and prognostic biomarkers as well as therapeutic targets in OSC.

Download Full-text

Inhibitory effect of sodium butyrate on colorectal cancer cells and construction of the related molecular network

BMC Cancer ◽

10.1186/s12885-021-07845-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yang Xi ◽

Zhuang Jing ◽

Wu Wei ◽

Zhang Chun ◽

Qi Quan ◽

...

Keyword(s):

Cell Proliferation ◽

Sodium Butyrate ◽

Molecular Network ◽

Differentially Expressed ◽

Cell Counting ◽

Molecular Networks ◽

Ppi Network ◽

Invasion And Metastasis ◽

Cerna Network ◽

Proliferation Ability

Abstract Background Sodium butyrate (NaB) is produced through the fermentation of dietary fiber that is not absorbed and digested by the small intestine. Purpose Here, we aimed to investigate the effects of NaB on the proliferation, invasion, and metastasis of CRC cells and their potential underlying molecular mechanism(s). Methods The cell counting kit-8 (CCK-8) assay and EdU assay were used to detect cell proliferation ability, flow cytometry was used to investigate the induction of apoptosis and cell cycle progression, and the scratch-wound healing and transwell assays were used to evaluate cell migration and invasion, respectively. The human CRC genome information for tissues and CRC cells treated with NaB obtained from the NCBI GEO database was reannotated and used for differential RNA analysis. Functional and pathway enrichment analyses were performed for differentially expressed lncRNAs and mRNAs. A protein-protein interaction (PPI) network for the hub genes was constructed using the Cytoscape software. Targeted miRNAs were predicted based on the lnCeDB database, and a ceRNA network was constructed using the Cytoscape software. The Kaplan-Meier method was used to analyze patient prognosis using the clinical information and exon-seq data for CRC obtained from the Broad Institute’s GDAC Firehose platform. Results NaB decreased the proliferation ability of CRC cells in a dose- and time-dependent manner. The number of apoptotic CRC cells increased with the increase in NaB concentrations, and NaB induced a G1 phase block in CRC cells. Moreover, NaB suppressed the migratory and invasive capabilities of CRC cells. There were 666 differentially expressed mRNAs and 30 differentially expressed lncRNAs involved in the CRC inhibition by NaB. The PPI network and ceRNA network were constructed based on the differentially expressed mRNAs and lncRNAs. Three differentially expressed mRNAs, including HMGA2, LOXL2, and ST7, were significantly correlated with the prognosis of CRC. Conclusion NaB induces the apoptosis and inhibition of CRC cell proliferation, invasion, and metastasis by modulating complex molecular networks. RNA prediction and molecular network construction need to be the focus of further research in this direction.

Download Full-text

A risk score model with five long non-coding RNAs for predicting prognosis in gastric cancer: an integrated analysis combining TCGA and GEO datasets

PeerJ ◽

10.7717/peerj.10556 ◽

2021 ◽

Vol 9 ◽

pp. e10556

Author(s):

Yiguo Wu ◽

Junping Deng ◽

Shuhui Lai ◽

Yujuan You ◽

Jing Wu

Keyword(s):

Gastric Cancer ◽

Risk Score ◽

Prognostic Value ◽

Therapeutic Targets ◽

The Cancer Genome Atlas ◽

Stage Ii ◽

Differentially Expressed ◽

Integrated Analysis ◽

Non Coding Rnas ◽

Score Model

Background Gastric cancer (GC) is one of the most common carcinomas of the digestive tract, and the prognosis for these patients may be poor. There is evidence that some long non-coding RNAs(lncRNAs) can predict the prognosis of patients with GC. However, few lncRNA signatures have been used to predict prognosis. Herein, we aimed to construct a risk score model based on the expression of five lncRNAs to predict the prognosis of patients with GC and provide new potential therapeutic targets. Methods We performed differentially expressed and survival analyses to identify differentially expressed survival-ralated lncRNAs by using GC patient expression profile data from The Cancer Genome Atlas (TCGA) database. We then established a formula including five lncRNAs to predict the prognosis of patients with GC. In addition, to verify the prognostic value of this risk score model, two independent Gene Expression Omnibus (GEO) datasets, GSE62254 (N = 300) and GSE15459 (N = 200), were employed as validation groups. Results Based on the characteristics of five lncRNAs, patients with GC were divided into high or low risk subgroups. The prognostic value of the risk score model with five lncRNAs was confirmed in both TCGA and the two independent GEO datasets. Furthermore, stratification analysis results showed that this model had an independent prognostic value in patients with stage II–IV GC. We constructed a nomogram model combining clinical factors and the five lncRNAs to increase the accuracy of prognostic prediction. Enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested that the five lncRNAs are associated with multiple cancer occurrence and progression-related pathways. Conclusion The risk score model including five lncRNAs can predict the prognosis of patients with GC, especially those with stage II-IV, and may provide potential therapeutic targets in future.

Download Full-text

Integrated analysis of two-lncRNA signature as a potential prognostic biomarker in cervical cancer: a study based on public database

PeerJ ◽

10.7717/peerj.6761 ◽

2019 ◽

Vol 7 ◽

pp. e6761 ◽

Cited By ~ 9

Author(s):

Wenjuan Wu ◽

Jing Sui ◽

Tong Liu ◽

Sheng Yang ◽

Siyi Xu ◽

...

Keyword(s):

Cervical Cancer ◽

Roc Curve ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Integrated Analysis ◽

Roc Curve Analysis ◽

Gynecological Malignancy ◽

Lncrna Expression

Background Cervical cancer (CC) is a common gynecological malignancy in women worldwide. Evidence suggests that long non-coding RNAs (lncRNAs) can be used as biomarkers in patients with CC. However, prognostic biomarkers for CC are still lacking. The aim of our study was to find lncRNA biomarkers which are able to predict prognosis in CC based on the data from The Cancer Genome Atlas (TCGA). Methods The patients were divided into three groups according to FIGO stage. Differentially expressed lncRNAs were identified in CC tissue compared to adjacent normal tissues based on a fold change >2 and <0.5 at P < 0.05 for up- and downregulated lncRNA, respectively. The relationship between survival outcome and lncRNA expression was assessed with univariate and multivariate Cox proportional hazards regression analysis. We constructed a risk score as a method to evaluate prognosis. We used receiver operating characteristic (ROC) curve and the area under curve (AUC) analyses to assess the diagnostic value of a two-lncRNA signature. We detected the expression levels of the two lncRNAs in 31 pairs of newly diagnosed CC specimens and paired adjacent non-cancerous tissue specimens, and also in CC cell lines. Finally, the results were statistically compared using t-tests. Results In total, 289 RNA sequencing profiles and accompanying clinical data were obtained. We identified 49 differentially expressed lncRNAs, of which two related to overall survival (OS) in CC patients. These two lncRNAs (ILF3-AS1 and RASA4CP) were found together as a single prognostic signature. Meanwhile, the prognosis of patients with low-risk CC was better and positively correlated with OS (P < 0.001). Further analysis showed that the combined two-lncRNA expression signature could be used as an independent biomarker to evaluate the prognosis in CC. qRT-PCR results were consistent with TCGA, confirming downregulated expression of both lncRNAs. Furthermore, upon ROC curve analysis, the AUC of the combined lncRNAs was greater than that of the single lncRNAs alone (0.723 vs 0.704 and 0.685), respectively; P < 0.05. Conclusions Our study showed that the two-lncRNA signature of ILF3-AS1 and RASA4CP can be used as an independent biomarker for the prognosis of CC, based on bioinformatic analysis.

Download Full-text

miR-192 Is Overexpressed and Promotes Cell Proliferation in Prostate Cancer

Medical Principles and Practice ◽

10.1159/000496206 ◽

2018 ◽

Vol 28 (2) ◽

pp. 124-132 ◽

Cited By ~ 5

Author(s):

Zhong-Jun Chen ◽

You-Ji Yan ◽

Hao Shen ◽

Jia-Jie Zhou ◽

Guang-Hua Yang ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Progression ◽

Bioinformatic Analysis ◽

The Cancer Genome Atlas ◽

Low Grade ◽

Functional Roles ◽

Normal Tissues ◽

Cancer Genome Atlas

Objective: Prostate cancer (PCa) is one of the most prevalent types of cancer among men worldwide. The incidence of PCa is increasing in China. Therefore, there is an urgent need to identify novel diagnostic and prognostic markers for PCa to improve the treatment of the disease. Methods: The Cancer Genome Atlas (TCGA) and GEO database were used to analyze the expression of miR-192, and the relationship between miR-192 and the clinical features of patients with PCa. Cell cycle and cell proliferation assay were used to detect the functional roles of miR-192 in PCa. Bioinformatic analysis for miR-192–5p was performed using gene ontology and KEGG analysis. Results: By analyzing the dataset of TCGA, we found that miR-192 was overexpressed in PCa samples compared to normal tissues and was upregulated in high-grade PCa compared to low-grade PCa. We also observed that higher miR-192 expression was associated with a shorter biochemical recurrence-free survival time. Our results also demonstrated that miR-192 promoted PCa cell proliferation and cell cycle progression. Conclusion: These results suggest that miR-192 may be considered for use as a potential diagnostic and therapeutic target of PCa.

Download Full-text

Identification of Key Iron Metabolism-Related Long Non-Coding RNAs in Hepatocellular Carcinoma Based on Bioinformatics Analysis

10.21203/rs.3.rs-754313/v1 ◽

2021 ◽

Author(s):

yu chen

Keyword(s):

Hepatocellular Carcinoma ◽

Iron Metabolism ◽

Cox Regression ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Roc Curve Analysis ◽

Cerna Network ◽

Kaplan Meier ◽

Non Coding Rnas

Abstract Background： The present study explored the regulatory mechanisms and functional roles of iron metabolism-related long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) and their potential impact on prognosis of HCC patients. Methods：RNA-seq data and clinical information of HCC samples and normal samples were downloaded from The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) portal. Iron metabolism-related genes were downloaded from Reactome database and AmiGo2 database. Differential expression and correlation analysis were performed to identify iron metabolism-related differentially expressed lncRNAs (DElncRNAs). Moreover, Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) analysis were used to screen the possible prognostic and diagnostic biomarkers of HCC. Results: A total of 20 differentially expressed and iron metabolism-related genes (DEIMRG) were identified by overlapping 3746 differentially expressed genes (DEGs) and 86 IMRGs. Next, ARHGAP11B, LINC00205, LINC00261 and SNHG12 were screened through Univariate Cox regression. Kaplan-Meier survival curves indicated that ARHGAP11B, LINC00205, LINC00261 and SNHG12 were related to overall survival (OS) in HCC patient in TCGA database. ARHGAP11B, LINC00205 and LINC00261 were finally identified as prognostic DEIMRGs related with OS of HCC patients after validate the survival results in ICGC portal. ARHGAP11B, LINC00205 and LINC00261 all achieved an AUC value of >0.80 in ROC curve analysis. Furthermore, LINC00205 was identified as independently prognostic factor by multivariate Cox analysis combined with clinicopathological factors. Moreover, a ceRNA network including 25 DEmRNAs, 15 DEmiRNA and 3 DElncRNAs was successfully constructed, based on prognostic DElncRNAs and key target miRNAs and mRNAs of them predicted by starBase database and miRwalk. The PPI network illustrated that CDC25A, CHEK1, CCNE2 and ANLN proteins interact more with other proteins. Conclusions: In the present study, we identified iron metabolism related LINC00205 as a prognostic and diagnostic biomarker and constructed a metabolism-related ceRNA network, which may contribute to the treatment of HCC.

Download Full-text

Elucidating another level of epigenetic regulation in osteoarthritis by identifying functional cis-acting long non-coding RNAs and their targets in articular cartilage

10.1101/2020.03.23.003020 ◽

2020 ◽

Author(s):

Marcella van Hoolwerff ◽

Paula I. Metselaar ◽

Margo Tuerlings ◽

H. Eka D. Suchiman ◽

Nico Lakenberg ◽

...

Keyword(s):

Regulatory Networks ◽

Differentially Expressed ◽

Sequencing Data ◽

Protein Coding ◽

Expression Levels ◽

Cis Acting ◽

Joint Replacement Surgery ◽

Replacement Surgery ◽

Antisense Lncrnas ◽

Non Coding Rnas

ABSTRACTObjectiveTo identify robustly differentially expressed long non-coding RNAs (lncRNAs) with osteoarthritis (OA) pathophysiology in cartilage. Moreover to explore potential target mRNAs by establishing co-expression networks, followed by functional validation.MethodsRNA sequencing was performed on macroscopically lesioned and preserved OA cartilage of patients who underwent a joint replacement surgery due to OA (N=98). Differential expression (DE) analysis was performed on lncRNAs that were annotated in GENCODE and Ensembl. To identify potential interactions, correlations were calculated between the identified DE lncRNAs and previously reported DE protein-coding genes in the same samples. Modulation of chondrocyte lncRNA expression was achieved using LNA GapmeRs.ResultsBy applying our in-house pipeline we identified 5,053 lncRNAs to be robustly expressed, of which 191 were FDR significant differentially expressed between lesioned and preserved OA cartilage. Upon integrating mRNA sequencing data, we showed that intergenic and antisense DE lncRNAs show high, positive correlations with their flanking, respectively, sense genes. To functionally validate this observation we selected P3H2-AS1, which was downregulated in primary chondrocytes, resulting in downregulation of P3H2 gene expression levels. As such, we can confirm that P3H2-AS1 regulates its sense gene P3H2.ConclusionBy applying an improved detection strategy, robustly differentially expressed lncRNAs in OA cartilage were detected. Integration of these lncRNAs with differential mRNA expression levels in the same samples showed insight into their regulatory networks. Our data signifies that intergenic, as well as antisense lncRNAs play an important role in regulating the pathophysiology of OA.

Download Full-text

A transcriptomic profile of topping responsive non-coding RNAs in tobacco roots (Nicotiana tabacum)

BMC Genomics ◽

10.1186/s12864-019-6236-6 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 4

Author(s):

Xi Chen ◽

Shuo Sun ◽

Fangjie Liu ◽

Enhui Shen ◽

Lu Liu ◽

...

Keyword(s):

Nicotiana Tabacum ◽

High Throughput Sequencing ◽

Potential Role ◽

Interaction Network ◽

Differentially Expressed ◽

Circular Rnas ◽

Biological Functions ◽

Non Coding Rnas ◽

Nicotine Biosynthesis ◽

Tobacco Roots

Abstract Background Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs), accomplish remarkable variety of biological functions. However, the composition of ncRNAs and their interactions with coding RNAs in modulating and controlling of cellular process in plants is largely unknown. Using a diverse group of high-throughput sequencing strategies, the mRNA, miRNA, lncRNA and circRNA compositions of tobacco (Nicotiana tabacum) roots determined and their alteration and potential biological functions in response to topping treatment analyzed. Results A total of 688 miRNAs, 7423 non-redundant lncRNAs and 12,414 circRNAs were identified, among which, some selected differentially expressed RNAs were verified by quantitative real-time PCR. Using the differentially expressed RNAs, a co-expression network was established that included all four types of RNAs. The number of circRNAs identified were higher than that of miRNAs and lncRNAs, but only two circRNAs were present in the co-expression network. LncRNAs appear to be the most active ncRNAs based on their numbers presented in the co-expression network, but none of them seems to be an eTM (endogenous Target Mimicry) of miRNAs. Integrated with analyses of sequence interaction, several mRNA-circRNA-miRNA interaction networks with a potential role in the regulation of nicotine biosynthesis were uncovered, including a QS-circQS-miR6024 interaction network. In this network miR6024 was significantly down-regulated, while the expression levels of its two targets, circQS and its host gene QS, were sharply increased following the topping treatment. Conclusions These results illustrated the transcriptomic profiles of tobacco roots, the organ responsible for nicotine biosynthesis. mRNAs always play the most important roles, while ncRNAs are also expressed extensively for topping treatment response, especially circRNAs are the most activated in the ncRNA pool. These studies also provided insights on the coordinated regulation module of coding and non-coding RNAs in a single plant biological sample. The findings reported here indicate that ncRNAs appear to form interaction complex for the regulation of stress response forming regulation networks with transcripts involved in nicotine biosynthesis in tobacco.

Download Full-text

Antisense lncRNA NNT-AS1 Promoted Esophageal Squamous Cell Carcinoma Progression by Regulating Its Sense Gene NNT Expression

10.21203/rs.3.rs-903062/v1 ◽

2021 ◽

Author(s):

Xianglong Pan ◽

Qi Wang ◽

Yue Yu ◽

Weibing Wu ◽

Liang Chen ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Differentially Expressed ◽

Rank Test ◽

Pathway Enrichment Analysis ◽

Antisense Lncrnas

Abstract BackgroundAntisense lncRNAs were endogenous productions from the antisense strand of coding genes and transcribed in the opposite direction of sense gene. This study aimed to systematically evaluate the roles and functions of antisense lncRNAs in esophageal squamous cell carcinoma (ESCC).MethodsDifferentially expressed antisense lncRNAs were initially screened using transcriptome data from 119 paired ESCC samples in GSE53624, and were further validated in 6 paired ESCC samples from our institution. Log-rank test was adopted to identify ESCC prognosis associated lncRNAs. Finally, functional assays were performed to reveal the functions of our identified antisense lncRNAs. ResultsIn total, 174 antisense lncRNAs were differentially expressed in both GSE53624 and JSPH samples. Five of them were significantly associated with ESCC prognosis (NNT-AS1, NKILA, CCDC18-AS1, SLCO4A1-AS1 and AC110619.1). The upregulation of NNT-AS1 was validated in ESCC cell lines. Knockdown of NNT-AS1 inhibited ESCC cell proliferation, migration, and promoted ESCC cells apoptosis and induced cell cycle arrest in G2/M stage. NNT-AS1 expression was significantly correlated with its sense gene NNT and NNT-AS1 knockdown could suppress NNT expression. Inhibition of NNT suppressed ESCC cell proliferation and migration. Mechanically, NNT-AS1 served as a competing endogenous RNA to sponge the miR-382-5p, which could repress NNT expression. Pathway enrichment analysis and western blot assay indicated that NNT-AS1 and NNT could regulate the cell cycle pathway. ConclusionAntisense lncRNA NNT-AS1 promoted ECSS progression by targeting NNT through sponging miR-382-5p. This study provided us a deeper insight into the roles of antisense lncRNAs in ESCC and identified potential therapeutic targets.

Download Full-text

N-linked Glycosylation Is Required for Optimal Function of Kaposi's Sarcoma Herpesvirus–encoded, but Not Cellular, Interleukin 6

Journal of Experimental Medicine ◽

10.1084/jem.20031205 ◽

2004 ◽

Vol 199 (4) ◽

pp. 503-514 ◽

Cited By ~ 22

Author(s):

Charles S. Dela Cruz ◽

Yoomi Lee ◽

Srinivas R. Viswanathan ◽

Ayman S. El-Guindy ◽

Jennifer Gerlach ◽

...

Keyword(s):

Cell Proliferation ◽

Interleukin 6 ◽

Kaposi's Sarcoma ◽

Kaposi’S Sarcoma ◽

Biological Functions ◽

Functional Roles ◽

Gp130 Receptor ◽

Optimal Function ◽

Dependent Cell ◽

Human Cytokine

Kaposi's sarcoma–associated herpesvirus interleukin-6 (vIL-6) is a structural and functional homologue of the human cytokine IL-6 (hIL-6). hIL-6 and vIL-6 exhibit similar biological functions and both act via the gp130 receptor subunit to activate the Janus tyrosine kinase (JAK)1 and signal transducer and activator of transcription (STAT)1/3 pathway. Here we show that vIL-6 is N-linked glycosylated at N78 and N89 and demonstrate that N-linked glycosylation at site N89 of vIL-6 markedly enhances binding to gp130, signaling through the JAK1-STAT1/3 pathway and functions in a cytokine-dependent cell proliferation bioassay. Although hIL-6 is also N-glycosylated at N73 and multiply O-glycosylated, neither N-linked nor O-linked glycosylation is necessary for IL-6 receptor α–dependent binding to gp130 or signaling through JAK1-STAT1/3. As distinct from vIL-6, unglycosylated hIL-6 is as potent as glycosylated hIL-6 in stimulating B cell proliferation. These findings highlight distinct functional roles of N-linked glycosylation in viral and cellular IL-6.

Download Full-text