Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

Razpotnik, Rok; Nassib, Petra; Kunej, Tanja; Rozman, Damjana; Režen, Tadeja

doi:10.3390/ijms22147477

Cited by 7 publications

(5 citation statements)

References 74 publications

(90 reference statements)

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“…Effective biomarkers can be used to predict patients' progress and formulate treatment plans, which is the key to accelerating the research process of precision treatment of BC 28 . Previous studies have shown that ESRP2 can directly or indirectly participate in the progression of various tumors by affecting splicing variation, EMT process, or interacting with upstream and downstream molecules [29][30][31][32][33] . Most of the reports about ESRP2 in BC only studied the relationship between ESRP2 and EMT, which affects the occurrence and development of BC, yet did not further analyze the role of ESRP2 expression and the related molecular mechanism 16,25,33 .…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of ESRP2 inhibits breast cancer cell proliferation via inhibiting cyclinD1

He,

Chen,

Zhang

et al. 2024

Preprint

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Background Epithelial splicing regulatory protein 2 (ESRP2),an important alternative splicing protein of mRNA, is reported to have a dual role in tumors, which can promote or inhibit the occurrence and development of tumors. However, the function and mechanism of ESRP2 in breast cancer (BC) remain unclear. Methods The distribution of ESRP2 expression in breast cancer and the correlation between ESRP2 expression and the overall survival rate were detected by The Cancer Genome Atlas (TCGA) database. Gene Ontology(GO)analysis, containing biological process, cellular components, and molecular function,was utilized to evaluate the potential mechanism of ESRP2 in breast cancer. The ESRP2 expression in breast cancer cell lines was detected by real-time quantitative PCR analysis (RT-qPCR) and western blotting. Cell clone was performed to examine the proliferation of ESRP2 knockdown in MCF-7 cells. The cell cycle was measured by flow cytometry assays. The role of ESRP2 knockdown in synergistic effect with chemotherapeutic agents was also determined by MTT assay. Results Bioinformatics analysis demonstrated that the ESRP2 gene was elevated in breast cancer cells and its overexpression was strongly correlated with shorter overall survival. GO analysis revealed that ESRP2 expression was related to cell proliferation. ESRP2 mRNA and protein expression were elevated in breast cancer cell lines, compared to the normal human breast cell line MCF-10A. Dwon-regulation of ESRP2 inhibited cell proliferation and promoted the sensitivity of chemotherapy drug, Cisplatin(DDP) and Paclitaxel (TAXOL), in MCF-7 cells.Additionally,ESRP2 knockdown obstructed the cell cycle at the G1 phase and caused a decrease in cyclinD1 protein expression. Conclusions These findings reveal that ESRP2 is highly expressed in breast cancer and is correlated with poor prognosis in breast cancer patients. ESRP2 knockdown can inhibit MCF-7 cell proliferation by arresting the cell cycle at the G1 phase and promoting the sensitivity of chemotherapy drugs (DDP and TAXOL)in MCF-7 cells. ESRP2 may be required for the regulation of breast cancer progression, as well as a critical target for the clinical treatment of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Down-regulation of ESRP2 inhibits breast cancer cell proliferation via inhibiting cyclinD1

He,

Chen,

Zhang

et al. 2024

Preprint

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“…YAP is a mechanosensitive transcription factor regulating organ size and tissue regeneration (Dong et al, 2007), dysregulation of which impairs normal hepatocellular regeneration pathways (Hyun et al, 2019). Recently, a role for ESRP2 in regulation of circRNA expression was described (Razpotnik et al, 2021). The authors found that ESRP2 depletion, alters the expression of candidate circRNA, that is involved in HCC pathogenesis.…”

Section: Mrna Splicingmentioning

confidence: 99%

Emerging roles of RNA‐binding proteins in fatty liver disease

Adesanya,

Das,

Kalsotra

2024

WIREs RNA

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A rampant and urgent global health issue of the 21st century is the emergence and progression of fatty liver disease (FLD), including alcoholic fatty liver disease and the more heterogenous metabolism‐associated (or non‐alcoholic) fatty liver disease (MAFLD/NAFLD) phenotypes. These conditions manifest as disease spectra, progressing from benign hepatic steatosis to symptomatic steatohepatitis, cirrhosis, and, ultimately, hepatocellular carcinoma. With numerous intricately regulated molecular pathways implicated in its pathophysiology, recent data have emphasized the critical roles of RNA‐binding proteins (RBPs) in the onset and development of FLD. They regulate gene transcription and post‐transcriptional processes, including pre‐mRNA splicing, capping, and polyadenylation, as well as mature mRNA transport, stability, and translation. RBP dysfunction at every point along the mRNA life cycle has been associated with altered lipid metabolism and cellular stress response, resulting in hepatic inflammation and fibrosis. Here, we discuss the current understanding of the role of RBPs in the post‐transcriptional processes associated with FLD and highlight the possible and emerging therapeutic strategies leveraging RBP function for FLD treatment.This article is categorized under: RNA in Disease and Development > RNA in Disease

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“…Features of the gene architecture, such as the composition of its pre‐mature RNA sequence (exon and intron lengths, RBP motifs, inverted repeats, and GC‐content) as well as its secondary structure (G‐quadruplex), along with epigenetic marks, influence back‐splicing decisions (Caba et al, 2021; Razpotnik et al, 2021; Wang et al, 2020; Zhang et al, 2014). By modulating the features of gene architecture, PARP1 can control the expression of circRNAs.…”

Section: Interplay Of Parp1 Binding Gene Architecture and Circrna Bio...mentioning

confidence: 99%

Exploring the interplay between PARP1 and circRNA biogenesis and function

Dhahri,

Fondufe‐Mittendorf

2023

WIREs RNA

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PARP1 (poly‐ADP‐ribose polymerase 1) is a multidomain protein with a flexible and self‐folding structure that allows it to interact with a wide range of biomolecules, including nucleic acids and target proteins. PARP1 interacts with its target molecules either covalently via PARylation or non‐covalently through its PAR moieties induced by auto‐PARylation. These diverse interactions allow PARP1 to participate in complex regulatory circuits and cellular functions. Although the most studied PARP1‐mediated functions are associated with DNA repair and cellular stress response, subsequent discoveries have revealed additional biological functions. Based on these findings, PARP1 is now recognized as a major modulator of gene expression. Several discoveries show that this multifunctional protein has been intimately connected to several steps of mRNA biogenesis, from transcription initiation to mRNA splicing, polyadenylation, export, and translation of mRNA to proteins. Nevertheless, our understanding of PARP1's involvement in the biogenesis of both coding and noncoding RNA, notably circular RNA (circRNA), remains restricted. In this review, we outline the possible roles of PARP1 in circRNA biogenesis. A full examination of the regulatory roles of PARP1 in nuclear processes with an emphasis on circRNA may reveal new avenues to control dysregulation implicated in the pathogenesis of several diseases such as neurodegenerative disorders and cancers.This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Processing > Splicing Regulation/Alternative Splicing

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Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

Cited by 7 publications

References 74 publications

Down-regulation of ESRP2 inhibits breast cancer cell proliferation via inhibiting cyclinD1

Down-regulation of ESRP2 inhibits breast cancer cell proliferation via inhibiting cyclinD1

Emerging roles of RNA‐binding proteins in fatty liver disease

Exploring the interplay between PARP1 and circRNA biogenesis and function

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