Ancient and modern: hints of a core post‐transcriptional network driving chemotherapy resistance in ovarian cancer

Blagden, Sarah P.; Mouti, Mai Abdel; Chettle, James

doi:10.1002/wrna.1432

Cited by 11 publications

(11 citation statements)

References 135 publications

(234 reference statements)

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“…RBPs regulate the expressions of genes required for many aspects of cancer behaviors including its sensitivity to chemotherapy in post-transcriptional network ( 37 ). In the identified five RBPs, the expressions of CELF4, LRRFIP2, ZNF385A, and PPARGC1A were down-regulated, while the expression of NOP14 was up-regulated (all P < 0.001).…”

Section: Conclusion and Discussionmentioning

confidence: 99%

A New RBPs-Related Signature Predicts the Prognosis of Colon Adenocarcinoma Patients

2021

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The dysregulation of RNA binding proteins (RBPs) is closely related to tumorigenesis and development. However, the role of RBPs in Colon adenocarcinoma (COAD) is still poorly understood. We downloaded COAD’s RNASeq data from the Cancer Genome Atlas (TCGA) database, screened the differently expressed RBPs in normal tissues and tumor, and constructed a protein interaction network. COAD patients were randomly divided into a training set (N = 315) and a testing set (N = 132). In the training set, univariate Cox analysis identified 12 RBPs significantly related to the prognosis of COAD. By multivariate COX analysis, we constructed a prognostic model composed of five RBPs (CELF4, LRRFIP2, NOP14, PPARGC1A, ZNF385A) based on the lowest Akaike information criterion. Each COAD patient was scored according to the model formula. Further analysis showed that compared with the low-risk group, the overall survival rate (OS) of patients in the high-risk group was significantly lower. The area under the curve of the time-dependent receiver operator characteristic (ROC) curve was 0.722 in the training group and 0.738 in the test group, which confirmed a good prediction feature. In addition, a nomogram was constructed based on clinicopathological characteristics and risk scores. C-index and calibration curve proved the accuracy in predicting the 1-, 3-, and 5-year survival rates of COAD patients. In short, we constructed a superior prognostic and diagnostic signature composed of five RBPs, which indicates new possibilities for individualized treatment of COAD patients.

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Section: Conclusion and Discussionmentioning

confidence: 99%

A New RBPs-Related Signature Predicts the Prognosis of Colon Adenocarcinoma Patients

2021

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“…Both MALAT1 and HOTAIR have been suggested as potential therapeutic targets to restore platinum sensitivity. The overexpression of PVT1 and HOTAIR were implicated in cisplatin resistance in cell line models by regulating apoptotic factors or activating the NF-κB (nuclear factor kappa B) pathway, respectively [ 75 , 76 ]. Intriguingly, increased levels of PVT1 after carboplatin-docetaxel treatment induced TP53 and TIMP1 (tissue inhibitor of metalloproteases-peptidase inhibitor 1) proteins expression concomitantly to decreased cell proliferation [ 77 ].…”

Section: Lncrnas and Their Association With Ovarian Cancermentioning

confidence: 99%

The Interplay between Long Noncoding RNAs and Proteins of the Epigenetic Machinery in Ovarian Cancer

Calanca

Abildgaard

Rainho

et al. 2020

Cancers

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Comprehensive large-scale sequencing and bioinformatics analyses have uncovered a myriad of cancer-associated long noncoding RNAs (lncRNAs). Aberrant expression of lncRNAs is associated with epigenetic reprogramming during tumor development and progression, mainly due to their ability to interact with DNA, RNA, or proteins to regulate gene expression. LncRNAs participate in the control of gene expression patterns during development and cell differentiation and can be cell and cancer type specific. In this review, we described the potential of lncRNAs for clinical applications in ovarian cancer (OC). OC is a complex and heterogeneous disease characterized by relapse, chemoresistance, and high mortality rates. Despite advances in diagnosis and treatment, no significant improvements in long-term survival were observed in OC patients. A set of lncRNAs was associated with survival and response to therapy in this malignancy. We manually curated databases and used bioinformatics tools to identify lncRNAs implicated in the epigenetic regulation, along with examples of direct interactions between the lncRNAs and proteins of the epigenetic machinery in OC. The resources and mechanisms presented herein can improve the understanding of OC biology and provide the basis for further investigations regarding the selection of novel biomarkers and therapeutic targets.

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“…Prior studies showed that RBPs could regulate the functions of lncRNAs and coding genes through direct interactions with these RNA transcripts [31,32]. Thus, RBPs that had the probability to bind with RMRP and ZNRF3 mRNA were screened out through POSTAR database.…”

Section: Rmrp Regulated Znrf3 Expression and Mrna Stability Through Rmentioning

confidence: 99%

“…After 3 h of co-incubation, the optical density (OD) values were measured at 450 nm using the SpectraMax 190 microplate reader (Molecular Device, San Jose, CA, USA). For the measurement of cell survival rate, transfected cells (100µl/well) were seeded into 96-well plates for 24 h and then treated with different concentrations (8,16,32,64,128, or 256 µM) of TMZ for another 24 h. Next, 10µl of CCK-8 solution was added into each well. Three hours later, OD values were determined at 450 nm, followed by the determination of 50% inhibitory concentration (IC 50 ).…”

Section: Cck-8 Assaymentioning

confidence: 99%

A Positive Feedback Loop of lncRNA-RMRP/ZNRF3 axis and Wnt/β-catenin Signaling Regulates Temozolomide Resistance in Glioma

Han

et al. 2020

Preprint

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Background: Drug resistance strikingly limits the therapeutic effect of temozolomide (TMZ) (a common drug for glioma). Long non-coding RNA (lncRNA) RMRP was found to be implicated in glioma progression. However, the effects of RMRP on TMZ resistance along with related molecular mechanisms are poor defined in glioma. Methods: RMRP, ZNRF3, and IGF2BP3 were screened out by bioinformatics analysis. The expression levels of lncRNAs and mRNAs were measured by RT-qPCR assay. Protein levels of genes were detected by western blot and immunofluorescence assays. ZNRF3 mRNA stability was analyzed using Actinomycin D assay. Cell proliferative ability and survival rate were determined by CCK-8 assay. Cell apoptotic patterns were estimated by flow cytometry. The effects of RMRP knockdown on the growth of TMZ-treated glioma xenograft tumors were explored in vivo. The relationships among IGF2BP3, RMRP and ZNRF3 were explored by bioinformatics prediction analysis, RNA immunoprecipitation and RNA pull-down assays. Results: RMRP was highly expressed in glioma. RMRP knockdown curbed cell proliferation, facilitated cell apoptosis and reduced TMZ resistance in glioma cells and hindered the growth of TMZ-treated glioma xenograft tumors. RMRP exerted its functions by down-regulating ZNRF3 in glioma cells. IGF2BP3 interacted with RMRP and ZNRF3 mRNA. RMRP reduced ZNRF3 expression and mRNA stability by IGF2BP3. RMRP knockdown inhibited β-catenin expression by up-regulating ZNRF3 and β-catenin promoted RMRP expression in glioma cells. Conclusion: RMRP/ZNRF3 axis and Wnt/β-catenin signaling formed a positive feedback loop to regulate TMZ resistance in glioma. The sustained activation of Wnt/β-catenin signaling by RMRP contributes the better management of cancers.

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Ancient and modern: hints of a core post‐transcriptional network driving chemotherapy resistance in ovarian cancer

Cited by 11 publications

References 135 publications

A New RBPs-Related Signature Predicts the Prognosis of Colon Adenocarcinoma Patients

A New RBPs-Related Signature Predicts the Prognosis of Colon Adenocarcinoma Patients

The Interplay between Long Noncoding RNAs and Proteins of the Epigenetic Machinery in Ovarian Cancer

A Positive Feedback Loop of lncRNA-RMRP/ZNRF3 axis and Wnt/β-catenin Signaling Regulates Temozolomide Resistance in Glioma

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