Analysis of lncRNA, miRNA and mRNA-associated ceRNA networks and identification of potential drug targets for drug-resistant non-small cell lung cancer

Kong, Xiangzhen; Hu, Shousen; Yuan, Yanggang; Du, Yue; Zhu, Zhaowei; Song, Zhizhen; Lu, Shanshan; Zhao, Chang; Yan, Dan

doi:10.7150/jca.40729

Cited by 28 publications

(19 citation statements)

References 47 publications

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“…To understand and identify potential therapeutic targets for PTC, we discussed the pathogenesis of PTC and use the interaction between differentially expressed RNA groups to constitute the ceRNA network of PTC. The ceRNA network hypothesis explains the relationship between lncRNAs, miRNAs, and mRNAs (14), nds genes that are sequentially up-regulated in tissues, classical PTC tissues, and highly cellular PTC tissues, and derives the possible mechanism of tumor malignant phenotype evolution of PTC.…”

Section: Discussionmentioning

confidence: 99%

lncRNA-miRNA-mRNA ceRNA Network in Thyroid Carcinoma from The Cancer Genome Atlas

Mo¹,

Jiang²,

Wang³

et al. 2020

Preprint

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Increasing evidence indicates that the competitive endogenous RNA (ceRNA) hypothesis, that is, long non-coding RNA (LncRNA) can competitively bind microRNA (miRNA) through miRNA response elements to affect the expression of target RNA, and dysregulation of LncRNA expression plays a key role in tumor progression. The papillary thyroid carcinoma that we studied is the most significant pathological type of thyroid cancer, but its ceRNA network has not been extensively evaluated. We analyzed level-3 data from RNA-Seq of 58 para-carcinoma tissues and 501 patients with primary papillary thyroid carcinoma (PTC) using the DEseq software package and downloaded clinical information from The Cancer Genome Atlas (TCGA) to find potential biomarkers or therapeutic targets. As a result, 149 differential miRNAs were selected, including 117 up -regulated, 32 down-regulated, and 3099 differential mRNAs, including 1976 up-regulated, 1123 down-regulated, and 434 differential lncRNAs, including 331 up-regulated and 103 down-regulated (Fold Change > 2, P < 0.05). The interactions between these differentially expressed RNA groups constitute the ceRNA network of PTC. Moreover, we used the microde database to predict the miRNAs that may be acted by the above screened differential lncRNAs and intersected with the selected miRNAs, and further predicted the target genes of the intersecting miRNAs by TargetScan, miRTarBase and miRDB, and intersected with the selected mRNAs. From the constructed ceRNA network we can see that Linc00460 may cause the invasion and metastasis of PTC by competitively inhibiting hsa-mir-150 and upregulating the expression of its downstream target gene EREG. Our study identified a series of lncRNAs associated with PTC progression and prognosis, and this complex ceRNA interaction network provides guidance for better understanding of the molecular mechanisms of PTC and can be used as an effective diagnostic tool for PTC invasion, metastasis and prognosis. Kaplan-Meier analysis of the differentially expressed RNAs associated with PTC pathogenesis confirmed that the lncRNAs AC097717.1, C20orf203, EMX2OS were potentially associated with the prognosis of PTC (P<0.05).

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Section: Discussionmentioning

confidence: 99%

lncRNA-miRNA-mRNA ceRNA Network in Thyroid Carcinoma from The Cancer Genome Atlas

Mo¹,

Jiang²,

Wang³

et al. 2020

Preprint

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“…The relationship between DElncRNAs and DEmiRNAs was explored by the database starBase v3.0 based on CLIP-seq data research and the database miRcode based on the GENCODE database ( Kong et al, 2020 ). TargetScan, miRcode and MiRanda were further used to decode the interaction between DEmiRNAs and DEmRNAs.…”

Section: Methodsmentioning

confidence: 99%

Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR

Liu

Wang

et al. 2021

PeerJ

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Background Drug resistance is the main obstacle in the treatment of leukemia. As a member of the competitive endogenous RNA (ceRNA) mechanism, underlying roles of lncRNA are rarely reported in drug-resistant leukemia cells. Methods The gene expression profiles of lncRNAs and mRNAs in doxorubicin-resistant K562/ADR and sensitive K562 cells were established by RNA sequencing (RNA-seq). Expression of differentially expressed lncRNAs (DElncRNAs) and DEmRNAs was validated by qRT-PCR. The potential biological functions of DElncRNAs targets were identified by GO and KEGG pathway enrichment analyses, and the lncRNA-miRNA-mRNA ceRNA network was further constructed. K562/ADR cells were transfected with CCDC26 and LINC01515 siRNAs to detect the mRNA levels of GLRX5 and DICER1, respectively. The cell survival rate after transfection was detected by CCK-8 assay. Results The ceRNA network was composed of 409 lncRNA-miRNA pairs and 306 miRNA-mRNA pairs based on 67 DElncRNAs, 58 DEmiRNAs and 192 DEmRNAs. Knockdown of CCDC26 and LINC01515 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the half-maximal inhibitory concentration (IC50) of doxorubicin. Furthermore, knockdown of GLRX5 and DICER1 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the IC50 of doxorubicin. Conclusions The ceRNA regulatory networks may play important roles in drug resistance of leukemia cells. CCDC26/miR-140-5p/GLRX5 and LINC01515/miR-425-5p/DICER1 may be potential targets for drug resistance in K562/ADR cells. This study provides a promising strategy to overcome drug resistance and deepens the understanding of the ceRNA regulatory mechanism related to drug resistance in CML cells.

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“…We predicted DE-miRNA target lncRNA using miRWalk2.0 (http://zmf.umm.uni-heidelberg.de/ apps/zmf/mirwalk2/index.html). We selected miRWalk, TargetScan, and RNAhybrid to decode the relationships between the differentially expressed miRNAs and lncRNAs (22). According to the ceRNA regulatory mechanism and the changing trends of lncRNAs, miRNAs, and mRNAs, we constructed a ceRNA regulatory network using Cytoscape 3.6.1.…”

Section: Bioinformatics Analysismentioning

confidence: 99%

Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer

Chen

Shen

et al. 2021

Front. Oncol.

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Ivosidenib is an isocitrate dehydrogenase mutant inhibitor that the US Food and Drug Administration recently approved for the treatment of leukemia. Studies suggested that ivosidenib may inhibit the progression of non-small cell lung cancer (NSCLC). In the present study, we explored RNAs and their potential regulatory mechanisms by which ivosidenib treats NSCLC cells. We used MTT assays, Transwell assays, and flow cytometry to measure the anti-tumor effects of ivosidenib in NSCLC cells. We performed whole transcriptome sequencing to determine differentially expressed mRNAs (DE-mRNAs) and non-coding RNAs (ncRNA). We used GO and KEGG pathway enrichment analyses to identify the functions and potential mechanisms. According to miRNA target interactions, we constructed a competing endogenous network. Ivosidenib inhibited the proliferation, invasion, and migration of NSCLC cells and inhibited tumor growth in vivo. We identified 212 DE-mRNAs, four DE-miRNAs, and 206 DE-lncRNAs in ivosidenib-treated NSCLC cells compared to untreated NSCLC cells. DE-mRNAs were significantly enriched in the cancer-associated pathways, including the TGF-β signaling pathway, the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, the MAPK signaling pathway, the Rap1 signaling pathway, and cell adhesion molecules. Based on the competing endogenous RNA hypothesis, we constructed lncRNA-miRNA-mRNA networks to elucidate the regulatory relationships between mRNA and ncRNA. We found that qRT-PCR results showed corresponding expression trends of differential genes with sequencing data. Our results provide insights into the molecular basis of ivosidenib suppression of NSCLC.

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Analysis of lncRNA, miRNA and mRNA-associated ceRNA networks and identification of potential drug targets for drug-resistant non-small cell lung cancer

Cited by 28 publications

References 47 publications

lncRNA-miRNA-mRNA ceRNA Network in Thyroid Carcinoma from The Cancer Genome Atlas

lncRNA-miRNA-mRNA ceRNA Network in Thyroid Carcinoma from The Cancer Genome Atlas

Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR

Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer

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