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

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.

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Identification of Potentially Functional Circular RNAs hsa_circ_0070934 and hsa_circ_0004315 as Prognostic Factor of Hepatocellular Carcinoma by Integrated Bioinformatics Analysis

10.21203/rs.3.rs-948198/v1 ◽

2021 ◽

Author(s):

Pejman Morovat ◽

Saman Morovat ◽

Arash M. Ashrafi ◽

Shahram Teimourian

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Prognostic Factor ◽

Sequence Data ◽

Functional Enrichment ◽

Differentially Expressed ◽

Circular Rnas ◽

Ppi Network ◽

Hub Genes ◽

Cerna Network

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, which has a high mortality rate and poor treatment outcomes with yet unknown molecular basis. It seems that gene expression plays a pivotal role in the pathogenesis of the disease. Circular RNAs (circRNAs) can interact with microRNAs (miRNAs) to regulate gene expression in various malignancies by acting as competitive endogenous RNAs (ceRNAs). However, the potential pathogenesis roles of the ceRNA network among circRNA/miRNA/mRNA in HCC are unclear. In this study, first, the HCC circRNA expression data were obtained from three Gene Expression Omnibus microarray datasets (GSE164803, GSE94508, GSE97332), and the differentially expressed circRNAs (DECs) were identified using R limma package. Also, the liver hepatocellular carcinoma (LIHC) miRNA and mRNA sequence data were retrieved from TCGA, and differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) were determined using the R DESeq2 package. Second, CSCD website was used to uncover the binding sites of miRNAs on DECs. The DECs' potential target miRNAs were revealed by conducting an intersection between predicted miRNAs from CSCD and downregulated DEMIs. Third, some related genes were uncovered by intersecting targeted genes predicted by miRWalk and targetscan online tools with upregulated DEGs. The ceRNA network was then built using the Cytoscape software. The functional enrichment and the overall survival time of these potential targeted genes were analyzed, and a PPI network was constructed in the STRING database. Network visualization was performed by Cytoscape, and ten hub genes were detected using the CytoHubba plugin tool. Four DECs (hsa_circ_0000520, hsa_circ_0008616, hsa_circ_0070934, hsa_circ_0004315) were obtained and six miRNAs (hsa-miR-542-5p, hsa-miR-326, hsa-miR-511-5p, hsa-miR-195-5p, hsa-miR-214-3p, and hsa-miR-424-5p) which are regulated by the above DECs were identified. Then 543 overlapped genes regulated by six miRNAs mentioned above were predicted. Functional enrichment analysis showed that these genes are mostly associated with cancer regulation functions. Ten hub genes (TTK،AURKB, KIF20A، KIF23، CEP55، CDC6، DTL، NCAPG، CENPF، PLK4) have been screened from the PPI network of the 204 survival-related genes. KIF20A, NCAPG, TTK, PLK4, and CDC6 were selected for the highest significant p-values. In the end, a circRNA-miRNA-mRNA regulatory axis was established for five final selected hub genes. This study implies the potential pathogenesis of the obtained network and proposes that the two DECs (has_circ_0070934 and has_circ_0004315) may be important prognostic factor for HCC.

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Identification of Three lncRNAs as Potential Predictive Biomarkers of Lung Adenocarcinoma

BioMed Research International ◽

10.1155/2020/7573689 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Donghui Jin ◽

Yuxuan Song ◽

Yuan Chen ◽

Peng Zhang

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Predictive Biomarkers ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Protein Kinase Activity ◽

Ppi Network ◽

Survival Analyses ◽

Normal Tissues ◽

Cerna Network

Background. Lung cancer is the most common cancer and the most common cause of cancer-related death worldwide. However, the molecular mechanism of its development is unclear. It is imperative to identify more novel biomarkers. Methods. Two datasets (GSE70880 and GSE113852) were downloaded from the Gene Expression Omnibus (GEO) database and used to identify the differentially expressed genes (DEGs) between lung cancer tissues and normal tissues. Then, we constructed a competing endogenous RNA (ceRNA) network and a protein-protein interaction (PPI) network and performed gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and survival analyses to identify potential biomarkers that are related to the diagnosis and prognosis of lung cancer. Results. A total of 41 lncRNAs and 805 mRNAs were differentially expressed in lung cancer. The ceRNA network contained four lncRNAs (CLDN10-AS1, SFTA1P, SRGAP3-AS2, and ADAMTS9-AS2), 21 miRNAs, and 48 mRNAs. Functional analyses revealed that the genes in the ceRNA network were mainly enriched in cell migration, transmembrane receptor, and protein kinase activity. mRNAs DLGAP5, E2F7, MCM7, RACGAP1, and RRM2 had the highest connectivity in the PPI network. Immunohistochemistry (IHC) demonstrated that mRNAs DLGAP5, MCM7, RACGAP1, and RRM2 were upregulated in lung adenocarcinoma (LUAD). Survival analyses showed that lncRNAs CLDN10-AS1, SFTA1P, and ADAMTS9-AS2 were associated with the prognosis of LUAD. Conclusion. lncRNAs CLDN10-AS1, SFTA1P, and ADAMTS9-AS2 might be the biomarkers of LUAD. For the first time, we confirmed the important role of lncRNA CLDN10-AS1 in LUAD.

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Identification of TIMP2 and RAX as key regulators in chemosensitive osteosarcoma

10.21203/rs.3.rs-47947/v1 ◽

2020 ◽

Author(s):

HuaBin Wang ◽

Yuanxiang Liu ◽

Haitao Zeng

Keyword(s):

Cell Proliferation ◽

Cell Survival ◽

Differentially Expressed ◽

Cell Counting ◽

Regulation Mechanism ◽

Rt Pcr ◽

P Values ◽

Vegf Signaling ◽

Differentially Expressed Mirnas ◽

And Function

Abstract Background This study is trying to investigate the regulation mechanism of chemosensitive osteosarcoma. mRNA and miRNA profiles were explored between chemosensitive and chemoresistant osteosarcoma patients based on GSE39058 dataset. IPA was used for pathway and function enrichment. Another dataset GSE21257 with clinical characteristics was used for survival analysis, and 68 new enrolled osteosarcoma patients with chemotherapy responses were used for RT-PCR validation. Finally, lentiviruses infected U-2 OS cells were subjected to cell counting and real-time cell analyzer.Results A total of 567 differentially expressed genes and 34 differentially expressed miRNAs were screened out. These genes mainly involved in the biology functions of cell survival and cell proliferation, and enriched in the pathways of VEGF signaling, Paxillin signaling, and Inhibition of matrix matalloproteases. In 53 validation osteosarcoma patients from GSE21257, high-expression of TIMP2 and BAX, two common genes among the enriched biology functions, have favorable prognosis with p-values 0.052 and 0.027 respectively. In the 68 new enrolled patients, both TIMP2 and BAX were RT-PCR validated to be high-expressed in chemosensitive group with p-values 0.04 and 0.003 respectively. In addition, cell count and cell index either in TIMP2 or BAX infected U-2 OS cells were smaller compared with control cells within four consecutive days.Conclusions In summary, the biology functions of cell survival and cell proliferation were identified to be mainly inhibited in chemosensitive osteosarcoma patients. Two up-regulated genes, TIMP2 and BAX, were validated to be important regulators of cell proliferation and cell apoptosis in chemosensitive group. Further experimental evidences are still needed to consolidate this results.

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LncRNA-mRNA Expression Profiles and Functional Networks Associated with Cognitive Impairment in Folate-deficient Mice

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210208110517 ◽

2021 ◽

Vol 24 ◽

Author(s):

Xiaojin Feng ◽

Fenfang Zhan ◽

Jialing Hu ◽

Fuzhou Hua ◽

Guohai Xu

Keyword(s):

Gene Expression ◽

Cognitive Impairment ◽

Mrna Expression ◽

Expression Profiles ◽

Differentially Expressed ◽

Functional Networks ◽

Ppi Network ◽

Hub Genes ◽

Cerna Network ◽

Deficient Mice

Background: Cognitive impairment is a common neurocognitive disorder that affects millions of worldwide people’s health,related tofolate deficiency. Objective: The present study aimed to investigate the lncRNA-mRNA functional networks associated with cognitive impairment in folate-deficient mice and elucidate their possible molecular mechanisms. Methods: We downloaded the gene expression profile (GSE148126) of lncRNAs and mRNAs from NCBI Gene Expression Omnibus (GEO) database. Four groups of mouse hippocampi were analyzed, including 4 months (4mo) and 18 months (18mo) of folic acid (FA) deficiency/supplementation. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified using gplots and heatmap packages. The functions of the DEmRNAs were evaluated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The hub genes wereidentified by CytoHubba plugins of Cytoscape, and protein-protein interaction (PPI) network of deregulated mRNAs was performed using STRING database. Finally, lncRNA-mRNA co-expression and competitive endogenous RNA (ceRNA) network analyses were constructed. Results: In total, we screened 67 lncRNAs with 211 mRNAs, and 89 lncRNAs with 229 mRNAs were differentially expressed in 4mo_FAand 18mo_FA deficient mice, respectively. GO analyses indicated that DEmRNAs were highly related to terms involved in binding and biological regulation. KEGG pathway analyses demonstrated that these genes were significantly enriched for Renin secretion, Pancreatic secretion and AMPK signaling pathways in 18mo_FA deficiency group. Subsequently, the top 5 hub genes werescreened from the PPI network, which may be key genes with the progression of folate deficiency. Upon the lncRNA-mRNA co-expression network analysis, we identified the top 10 lncRNAs having the maximum number of connections with related mRNAs. Finally, a ceRNA network was constructed for DE lncRNAs and DEmRNAs, and several pivotal miRNAs were predicted. Conclusions: This study identified the lncRNA-mRNA expression profiles and functional networks associated with cognitive impairment in folate-deficient mice, which provided support for the possible mechanisms and therapy for this disease.

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Comprehensive Analysis of LncRNAs Role in Tumorigenesis of Colon Adenocarcinoma

10.21203/rs.2.20479/v1 ◽

2020 ◽

Author(s):

Arash Poursheikhani ◽

Mohammad Reza Abbaszadegan ◽

Negin Nokhandani ◽

Mohammad Amin Kerachian

Keyword(s):

Colon Adenocarcinoma ◽

Differentially Expressed ◽

Rank Test ◽

Ppi Network ◽

R Software ◽

Cerna Network ◽

Kaplan Meier ◽

Limma Package ◽

Underlying Mechanisms ◽

Canonical Processes

Abstract Background Colon adenocarcinoma (COAD) is one of the most common gastrointestinal cancers globally. Molecular aberrations of tumor suppressors and/or oncogenes are the main contributors to its tumorigenesis. However, the exact underlying mechanisms of COAD pathogenesis are not clear yet. Thus, there is an urgent need to indicate promising potential diagnostic and prognostic biomarkers in COAD patients. In the current study, level 3 RNA-seq and miR-seq data and corresponding clinical data of colon adenocarcinoma (COAD) were retrieved from the TCGA database.The “limma” package in R software was utilized to indicate the differentially expressed genes. For in silico functional analysis, GO and KEGG signaling pathways were conducted. PPI network was constructed based on the STRING online database by Cytoscape 3.7.2. A ceRNA network was also constructed by “GDCRNATools” package in R software. Kaplan-Meier survival analysis (log-rank test) was used to indicate the relation between RNA expressions with patient’s survival time.Results The differential expression data demonstrated that 1512 mRNAs, 188 lncRNAs, and 329 miRNAs were differentially expressed in COAD. The GO and KEGG pathway analysis indicated that the differentially expressed mRNAs were primarily enriched in canonical processes in cancer. The PPI network showed that the PPARGC1A, ADAMTS5, PTGS2, FGFR2, TBX1, TWIST1, KIT, BDNF and MET proteins were the critical hubs. The Kaplan-Meier analysis revealed that 128 mRNAs, 15 lncRNAs, and 39 miRNAs were associated with overall survival time in the patients. The ceRNA network data demonstrated that three lncRNA including MAGI2-AS3, NEAT1, and SNHG3 genes were involved in the development of COAD.Conclusions Altogether, we integrated differentially expressed mRNAs, lncRNAs, and miRNAs in COAD bioinformatically. Our data suggested promising lncRNAs in the diagnosis and prognosis of patients with COAD.

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A Three-Gene Prognostic Signature Based on Circular RNA-Associated Competing Endogenous RNA Network for Patients with Lung Adenocarcinoma

10.21203/rs.3.rs-84423/v1 ◽

2020 ◽

Author(s):

Xuelong Wang ◽

Bin Zhou ◽

Yuxin Xia ◽

Jianxin Zuo ◽

Yanchao Liu ◽

...

Keyword(s):

Regulatory Mechanism ◽

Cox Regression ◽

Differentially Expressed ◽

Ppi Network ◽

Prognostic Signature ◽

Competing Endogenous Rna ◽

Cox Regression Analysis ◽

Prognostic Performance ◽

Cerna Network ◽

Lasso Method

Abstract Background: Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, functions of circRNAs in lung adenocarcinoma (LUAD) are still unknown. It is necessary to investigate the regulatory mechanism of circRNAs based on competing endogenous RNA (ceRNA) network in LUAD procession and further construct a prognostic signature for predicting overall survival of LUAD patients.Methods: Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed mRNAs (DEmRNAs) were selected to construct the ceRNA network based on TargetScan prediction tool and Pearson correlation coefficient. Functional and pathway enrichment analysis were performed using DAVID database. A PPI network was constructed and then visualized by Cytoscape software. Finally, we constructed a prognostic signature for LUAD patients using LASSO method and assessed the prognostic performance in the validation cohort.Results: A total of 38 DEcircRNAs, 56 DEmiRNAs, and 960 DEmRNAs were identifed. Based on the interactions predicted by TargetScan, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs and 49 DEmRNAs. GO and KEGG pathway analysis indicated that the circRNA-associated ceRNA network might be involved in regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a PPI network containing 12 DEmRNAs was constructed. Univariate cox regression analysis showed that three DEmRNAs were significantly associated with overall survival. Therefore, we constructed a three-gene prognostic signature for LUAD patients using LASSO method. By applying the signature, patients in the training cohort could be categorized into high-risk or low-risk subgroup with significant survival difference (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009). The prognostic performance was confirmed in an independent GEO cohort (HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004). Multivariate cox regression analysis proved that the three-gene signature was an independent prognostic factor for LUAD.Conclusions: Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and constructed a prognostic signature that could be a useful guide for personalized treatment of LUAD patients.

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

10.21203/rs.3.rs-770129/v2 ◽

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. Conclusions: We predicted the biological functions of many lncRNAs, which may serve as diagnostic and prognostic biomarkers as well as therapeutic targets in OSC.

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Downregulation of microRNA-586 Inhibits Proliferation, Invasion and Metastasis and Promotes Apoptosis in Human Osteosarcoma U2-OS Cell Line

Cytogenetic and Genome Research ◽

10.1159/000441073 ◽

2015 ◽

Vol 146 (4) ◽

pp. 268-278 ◽

Cited By ~ 4

Author(s):

Lei Yang ◽

Zong-Ming Liu ◽

Yan-Wei Rao ◽

Shao-Qian Cui ◽

Huan Wang ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Apoptosis ◽

Annexin V ◽

Cell Number ◽

Cell Counting ◽

Control Group ◽

Cell Cycle Distribution ◽

Invasion And Metastasis ◽

Blank Group ◽

Group Control Group

In this study, we aim to examine the association of microRNA-586 (miR-586) with osteosarcoma (OS) cell proliferation, apoptosis, invasion, and metastasis. U2-OS cell lines were divided into 4 groups: an miR-586 group, anti-miR-586 group, control group (empty plasmid) and blank group (no plasmid). qRT-PCR was used to detect miR-586 expression, cell counting kit-8 and EdU assays to detect cell proliferation, flow cytometry to detect cell cycle distribution, Annexin V/PI double staining to detect cell apoptosis, and the Transwell assay to detect cell invasion and metastasis. miR-586 expression was significantly higher in the miR-586 group but significantly lower in the anti-miR-586 group compared with the control and blank groups. Cell proliferation at 2-5 days after cell transfection and the EdU-positive cell number increased obviously in the miR-586 group but decreased clearly in the anti-miR-586 group. In the miR-586 group, cells at G0/G1 stage and apoptosis cells significantly decreased, while cells at G2/M and S stages and invasive and metastatic cells significantly increased compared to the control and blank groups; however, opposite trends were found in the anti-miR-586 group. Downregulation of miR-586 expression in OS may inhibit cell proliferation, invasion and metastasis, and promote cell apoptosis.

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Prognostic Nomogram Based on Circular RNA-Associated Competing Endogenous RNA Network For Patients With Lung Adenocarcinoma

10.21203/rs.3.rs-185751/v1 ◽

2021 ◽

Author(s):

Yang Li ◽

Rongrong Sun ◽

Rui Li ◽

Yonggang Chen ◽

He Du

Keyword(s):

Lung Adenocarcinoma ◽

Cancer Progression ◽

Pearson Correlation ◽

Functional Enrichment ◽

Differentially Expressed ◽

Circular Rnas ◽

Ppi Network ◽

Prognostic Signature ◽

Cerna Network ◽

Survival Difference

Abstract Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, function and application of circRNAs in lung adenocarcinoma (LUAD) are still unknown. In this study, we selected differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed mRNAs (DEmRNAs) to establish a circRNA-associated competitive endogenous RNA (ceRNA) network and further constructed a prognostic signature for LUAD patients. Based on TargetScan prediction tool and Pearson correlation coefficient, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs and 49 DEmRNAs. Functional enrichment indicated that the ceRNA network might be involved in regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a protein-protein interaction (PPI) network containing 12 DEmRNAs was constructed. Based on DEmRNAs within PPI network, we constructed a three-gene prognostic signature for LUAD patients using LASSO method. Patients in the training cohort could be categorized into high-risk or low-risk subgroup with significant survival difference (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009). The prognostic performance was confirmed in an independent cohort (HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004). Combining three-gene signature with clinical risk characters, a nomogram was constructed. The calibration curves for probability of 3- and 5-year overall survival showed significant agreement between nomogram predictions and actual observations. Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and constructed a prognostic signature that could be a useful guide for personalized treatment of LUAD patients.

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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.

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