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The functional role of long noncoding RNA in resistance to anticancer treatment.

ABSTRACT: Chemotherapy is one of the fundamental methods of cancer treatment. However, drug resistance remains the main cause of clinical treatment failure. We comprehensively review the newly identified roles of long noncoding RNAs (lncRNAs) in oncobiology that are associated with drug resistance. The expression of lncRNAs is tissue-specific and often dysregulated in human cancers. Accumulating evidence suggests that lncRNAs are involved in chemoresistance of cancer cells. The main lncRNA-driven mechanisms of chemoresistance include regulation of drug efflux, DNA damage repair, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT), induction of signaling pathways, and angiogenesis. LncRNA-driven mechanisms of resistance to various antineoplastic agents have been studied extensively. There are unique mechanisms of resistance against different types of drugs, and each mechanism may have more than one contributing factor. We summarize the emerging strategies that can be used to overcome the technical challenges in studying and addressing lncRNA-mediated drug resistance.

SUBMITTER: Qu Y

PROVIDER: S-EPMC7268113 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The functional role of long noncoding RNA in resistance to anticancer treatment.

Qu Yidi Y Tan Hor-Yue HY Chan Yau-Tuen YT Jiang Hongbo H Wang Ning N Wang Di D

Therapeutic advances in medical oncology 20200601

Chemotherapy is one of the fundamental methods of cancer treatment. However, drug resistance remains the main cause of clinical treatment failure. We comprehensively review the newly identified roles of long noncoding RNAs (lncRNAs) in oncobiology that are associated with drug resistance. The expression of lncRNAs is tissue-specific and often dysregulated in human cancers. Accumulating evidence suggests that lncRNAs are involved in chemoresistance of cancer cells. The main lncRNA-driven mechanis ...[more]

PMID: 32536982

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Project description:BACKGROUND:Differential gene expression analysis using RNA-seq data is a popular approach for discovering specific regulation mechanisms under certain environmental settings. Both gene ontology (GO) and KEGG pathway enrichment analysis are major processes for investigating gene groups that participate in common biological responses or possess related functions. However, traditional approaches based on differentially expressed genes only detect a few significant GO terms and pathways, which are frequently insufficient to explain all-inclusive gene regulation mechanisms. METHODS:Transcriptomes of survivin (birc5) gene knock-down experimental and wild-type control zebrafish embryos were sequenced and assembled, and a differential expression (DE) gene list was obtained for traditional functional enrichment analysis. In addition to including DE genes with significant fold-change levels, we considered additional associated genes near or overlapped with differentially expressed long noncoding RNAs (DE lncRNAs), which may directly or indirectly activate or inhibit target genes and play important roles in regulation networks. Both the original DE gene list and the additional DE lncRNA-associated genes were combined to perform a comprehensive overrepresentation analysis. RESULTS:In this study, a total of 638 DE genes and 616 DE lncRNA-associated genes (lncGenes) were leveraged simultaneously in searching for significant GO terms and KEGG pathways. Compared to the traditional approach of only using a differential expression gene list, the proposed method of employing DE lncRNA-associated genes identified several additional important GO terms and KEGG pathways. In GO enrichment analysis, 60% more GO terms were obtained, and several neuron development functional terms were retrieved as complete annotations. We also observed that additional important pathways such as the FoxO and MAPK signaling pathways were retrieved, which were shown in previous reports to play important roles in apoptosis and neuron development functions regulated by the survivin gene. CONCLUSIONS:We demonstrated that incorporating genes near or overlapped with DE lncRNAs into the DE gene list outperformed the traditional enrichment analysis method for effective biological functional interpretations. These hidden interactions between lncRNAs and target genes could facilitate more comprehensive analyses.

Project description:Long noncoding RNAs (lncRNAs) serve important roles in the biology of autoimmune diseases and immune‑associated disorders. To identify lncRNAs specifically associated with psoriasis, the expression of lncRNAs from biopsies obtained from patients with psoriasis were compared with samples obtained from healthy volunteers using a microarray. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect the expression of 10 identified dysregulated lncRNAs. Cis‑ and trans‑regulated target genes of lncRNAs were predicted. The results of microarray analysis indicated that 2,194 lncRNAs and 1,725 mRNAs were significantly dysregulated. Gene Ontology and pathway analyses among the dysregulated genes were performed. Co‑expression network analysis was also performed to study molecular interactions. Several identified pathways were associated with psoriasis. Among the 2,194 dysregulated lncRNAs, 1,549 of these had cis‑ or trans‑regulated predicted target genes. Among the 1,725 dysregulated mRNAs, 289 of the cis‑regulated target genes and 262 of the trans‑regulated target genes may be regulated by the differentially expressed lncRNAs; 10 differentially expressed lncRNAs were randomly selected and then validated. Of these lncRNAs, 7 exhibited the same expression profile as determined via microarray analysis, of which 3 lncRNAs were upregulated and 4 lncRNAs were downregulated. To the best of our knowledge, the present study is the first in which a microarray has been used to investigate the expression profile of lncRNAs associated with psoriasis. Additionally, the expression levels of the 10 aforementioned lncRNAs associated with psoriasis were validated in the present study for the first time using RT‑qPCR. The findings demonstrated that lncRNAs may contribute to the pathogenesis of psoriasis and suggested their potential diagnostic and therapeutic value. Furthermore, the findings of the present study suggest that the combined actions of several lncRNAs may contribute to the pathogenesis of psoriasis.

Dataset Information

The functional role of long noncoding RNA in resistance to anticancer treatment.

Publications

The functional role of long noncoding RNA in resistance to anticancer treatment.

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