Modulation of alternative splicing induced by paclitaxel in human lung cancer

Zhu, Zi-Ran; Chen, Dan; Zhang, Wenjing; Zhao, Jie; Zhi, Lili; Huang, Fang; Ji, Haoyu; Zhang, Jinrui; Liu, Han; Zou, Lijuan; Wang, Yan

doi:10.1038/s41419-018-0539-4

Cited by 23 publications

(13 citation statements)

References 26 publications

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“…Preliminary investigations revealed that AS perturbation was involved in the initiation and progression of several cancers [ [31] , [32] , [33] ]. In the present study, we identified prognosis-related AS events in ESAD, STAD, COAD, and READ patients.…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Gastrointestinal Pan-Adenocarcinomas

Lin

et al. 2018

EBioMedicine

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BackgroundGastrointestinal pan-adenocarcinomas, which mainly include adenocarcinomas of the esophagus, stomach, colon, and rectum, place a heavy burden on society owing to their poor prognoses. Since aberrant alternative splicing (AS) are starting to be considered as efficacious signatures for tumor prognosis predicting and therapeutic targets, systematic analysis of AS events is urgent.MethodsPrognosis-related AS events were selected by using univariate COX regression analysis. Gene functional enrichment analysis revealed the pathways enriched by prognosis-related AS. Then, prognostic signatures based on AS events were developed for prognosis prediction. Potential mechanism to regulate splicing events by splicing factors was analyzed via Pearson correlation and regulatory networks were constructed.FindingsA total of 967, 918, 674, and 406 AS events were identified as prognosis-related AS events in esophagus, stomach, colon, and rectum adenocarcinomas, respectively. Survival-associated AS events were distinguishing in the four subtypes of adenocarcinoma. Furthermore, computational algorithm results indicated that perturbation of ribosome and ubiquitin-mediated proteolysis pathways were the potential molecular mechanisms corresponding to inferior prognoses. Most notably, several prognostic signatures based on AS events displayed moderate performance in prognosis predicting. The area under curve values of the time-dependent receiver operating characteristic were 0.961, 0.871, 0.870, and 0.890 in esophagus, stomach, colon, and rectum adenocarcinomas. Survival-associated splicing factors were submitted to construct the AS regulatory network, which could be an underlying mechanism of AS events.InterpretationAS may could be ideal indiactors in the prognosis of gastrointestinal pan-adenocarcinomas. Exploring interesting splicing regulatory networks is conducive to solve the puzzles of AS.

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Section: Discussionmentioning

confidence: 99%

Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Gastrointestinal Pan-Adenocarcinomas

Lin

et al. 2018

EBioMedicine

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“…1D ). According to a recent study [ 16 ], paclitaxel inhibited mitosis by binding to microtubules and regulating mitosis-related pathways, including mitotic nuclear division, chromosome segregation, and G2/M transition of the mitotic cell cycle, in lung cancer cells. The results of our previous study on lung cancer cells showed that paclitaxel upregulated mitosis-related pathways, including mitotic nuclear division and chromosome segregation (unpublished data).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome analysis of iBET-151, a BET inhibitor alone and in combination with paclitaxel in gastric cancer cells

et al. 2020

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BET inhibitor, as an epigenetic regulator inhibitor, reduces the expression of oncogenes such as Myc and Bcl-2, which affects cancer growth and development. However, it has modest activity because of the narrow therapeutic index. Therefore, combination therapy is necessary to increase the anti-tumor effect. Paclitaxel, an anti-mitotic inhibitor, is used as second-line therapy for gastric cancer (GC) as a monotherapy or combination. In this study, we performed RNA sequencing of GC cells treated with iBET-151 and/or paclitaxel to identify the differentially expressed genes associated with possible mechanisms of synergistic effect. We also performed Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses to determine the most enriched terms and pathways of upregulated and downregulated genes. We found 460 genes in which iBET-151 and paclitaxel combination treatment changed more than single-treatment or no-treatment. Thus, additional functional studies are needed, but our results provide the first evidence of the synergistic effect between iBET-151 and paclitaxel in regulating the transcriptome of GC cells.

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“…The RNA sequencing results showed that RBM25 was involved in the regulation of multiple splicing events, including exon skipping and intron selection of retention and splice sites. RBM25 inhibits cell proliferation by inducing apoptosis and regulating the cell cycle in multiple cancers ( 31 , 32 ). However, the role of RBM25 in THCA has not been studied.…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Thyroid Carcinoma

Han

Yang

et al. 2021

Front. Oncol.

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Alternative splicing (AS) is a key mechanism involved in regulating gene expression and is closely related to tumorigenesis. The incidence of thyroid cancer (THCA) has increased during the past decade, and the role of AS in THCA is still unclear. Here, we used TCGA and to generate AS maps in patients with THCA. Univariate analysis revealed 825 AS events related to the survival of THCA. Five prognostic models of AA, AD, AT, ES, and ME events were obtained through lasso and multivariate analyses, and the final prediction model was established by integrating all the AS events in the five prediction models. Kaplan–Meier survival analysis revealed that the overall survival rate of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The ROC results revealed that the prognostic capabilities of each model at 3, 5, and 8 years were all greater than 0.7, and the final prognostic capabilities of the models were all greater than 0.9. By reviewing other databases and utilizing qPCR, we verified the established THCA gene model. In addition, gene set enrichment analysis showed that abnormal AS events might play key roles in tumor development and progression of THCA by participating in changes in molecular structure, homeostasis of the cell environment and in cell energy. Finally, a splicing correlation network was established to reveal the potential regulatory patterns between the predicted splicing factors and AS event candidates. In summary, AS should be considered an important prognostic indicator of THCA. Our results will help to elucidate the underlying mechanism of AS in the process of THCA tumorigenesis and broaden the prognostic and clinical application of molecular targeted therapy for THCA.

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Modulation of alternative splicing induced by paclitaxel in human lung cancer

Cited by 23 publications

References 26 publications

Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Gastrointestinal Pan-Adenocarcinomas

Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Gastrointestinal Pan-Adenocarcinomas

Transcriptome analysis of iBET-151, a BET inhibitor alone and in combination with paclitaxel in gastric cancer cells

Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Thyroid Carcinoma

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