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RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer.

ABSTRACT: The present study aimed to reveal the key long non-coding RNAs (lncRNAs) and the potential molecular mechanisms of XAV939 treatment in non-small cell lung cancer (NSCLC). The NSCLC cell line, NCI-H1299, was cultured with 10 µM XAV939 for 12 h, and NCI-H1299 cells without XAV939 treatment were used as controls. Following RNA isolation from the two groups, RNA-sequencing was performed to detect transcript expression levels, and differentially-expressed lncRNAs (DE-lncRNAs) and DE-genes (DEGs) were identified between groups and analyzed for their functions and associated pathways. The potential associations between proteins encoded by DEGs were revealed via a protein-protein interaction (PPI) network. Subsequently, the microRNA (miRNA/miR)-mRNA, lncRNA-miRNA and lncRNA-mRNA interactions were explored, followed by competing endogenous RNA (ceRNA) network construction. A total of 396 DEGs and 224 DE-lncRNAs were identified between the XAV939 and control groups. These lncRNAs were mainly enriched in pathways such as 'ferroptosis' [DEG, solute carrier family 7 member 11 (SLC7A11)]. The PPI network consisted of 97 nodes and 112 interactions. Furthermore, a total of 10 noteworthy lncRNAs were revealed in the DE-lncRNA-DEG interaction. Finally, the lncRNA-miRNA-mRNA regulatory association, including MIR503 host gene (MIR503HG)-miR1273c-SRY-box 4 (SOX4), was explored in the current ceRNA network. The downregulation of lncRNA MIR503HG induced by XAV939 may serve an important role in NSCLC suppression via sponging miR-1273c and regulating SOX4 expression. Furthermore, the downregulation of SLC7A11 induced by XAV939 may also inhibit the development of NSCLC via the ferroptosis pathway.

SUBMITTER: Yu H

PROVIDER: S-EPMC6507402 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer.

Yu Haixiang H Han Zhifeng Z Xu Zhenan Z An Chong C Xu Lei L Xin Hua H

Oncology letters 20190327 6

The present study aimed to reveal the key long non-coding RNAs (lncRNAs) and the potential molecular mechanisms of XAV939 treatment in non-small cell lung cancer (NSCLC). The NSCLC cell line, NCI-H1299, was cultured with 10 µM XAV939 for 12 h, and NCI-H1299 cells without XAV939 treatment were used as controls. Following RNA isolation from the two groups, RNA-sequencing was performed to detect transcript expression levels, and differentially-expressed lncRNAs (DE-lncRNAs) and DE-genes (DEGs) were ...[more]

PMID: 31186710

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Project description:The characteristic events in neurodegenerative diseases (NDDs) encompass protein misfolding, aggregation, accumulation, and their related cellular dysfunction, synaptic function loss. While distinct proteins are implicated in the pathological processes of different NDDs, the process of protein misfolding and aggregation remains notably similar across various conditions. Specifically, proteins undergo misfolding into beta-folded (β-folded) conformation, resulting in the formation of insoluble amyloid proteins. Despite advancements in comprehending protein aggregation, certain facets of this intricate process remain incompletely elucidated. In recent years, the concept that long non-coding RNAs (lncRNAs) contribute to protein aggregation has gained recognition. LncRNAs influence the formation of protein aggregates by facilitating protein overexpression through the regulation of gene transcription and translation, inhibiting protein degradation via lysosomal and autophagic pathways, and targeting aberrant modifications and phase transitions of proteins. A better understanding of the relationship between lncRNAs and aberrant protein aggregation is an important step in dissecting the underlying molecular mechanisms and will contribute to the discovery of new therapeutic targets and strategies. HIGHLIGHTS: NDDs are marked by protein misfolding, aggregation, and accumulation, leading to cellular dysfunction and loss of synaptic function. Despite different proteins being involved in various NDDs, the process of misfolding into β-folded conformations and forming insoluble amyloid proteins is consistent across conditions. The role of lncRNAs in protein aggregation has gained attention, as they regulate gene transcription and translation, inhibit protein degradation, and target aberrant protein modifications. Understanding the link between lncRNAs and protein aggregation is crucial for uncovering molecular mechanisms and developing new therapeutic targets.

Dataset Information

RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer.

Publications

RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer.

Similar Datasets

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