HNRNPA1, a Splicing Regulator, Is an Effective Target Protein for Cervical Cancer Detection: Comparison With Conventional Tumor Markers

Kim, Young-Jon; Kim, Byoung-Ryun; Ryu, Ji Won; Lee, Gyeong-Ok; Kim, Hak-Ryul; Choi, Keum-Ha; Ryu, Jae-Won; Na, Kyoung-Suk; Park, Min-Cheol; So, Hong-Seob; Cho, Ji-Hyun; Park, Do‐Sim

doi:10.1097/igc.0000000000000868

Cited by 17 publications

(11 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that UBC and HNRNPA1 participated in the biological process of CC. Studies have shown that ubiquitin-specific protease 7 could promote cervical carcinogenesis ( Su et al, 2018 ), while HNRNPA1 was a good diagnostic marker for cervical cancer ( Kim et al, 2017 ). Functional enrichment analysis found that these genes were mainly involved on the mitochondrion and lysosome-related pathways.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value and Potential Role of Alternative mRNA Splicing Events in Cervical Cancer

et al. 2020

View full text Add to dashboard Cite

Background: Increasing evidence suggests that aberrant alternative splicing (AS) events are associated with progression of cancer. This study evaluated the prognostic value and clarify the role of AS events in cervical cancer (CC). Methods: Based on RNA-seq AS event data and clinical information of CC patients in The Cancer Genome Atlas (TCGA) database, we sought to identify prognosisrelated AS events in this setting. We selected several survival-associated AS events to construct a prognostic predictor for CC through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression. Moreover, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were performed on genes with prognosis-related AS events and constructed an AS-splicing factors (SFs) regulatory network. Results: 2770 AS events were significantly correlated with overall survival (OS). The area under the curve (AUC) values of receiver-operator characteristic curve (ROC) for the final prognostic predictor were 0.926, 0.946 and 0.902 at 3, 5, and 10 years, respectively. These values indicated efficiency in prognostic risk stratification for patients with CC. The final prognostic predictor was an independent predictor of OS (HR: 1.24; 95% CI: 1.020-1.504; P < 0.05). The AS-SFs correlation network may reveal an underlying regulatory mechanism of AS events. Conclusion: AS events are essential participants in the prognosis of CC and hold great potentials for the prognostic stratification and development of treatment strategy.

show abstract

Section: Discussionmentioning

confidence: 99%

Prognostic Value and Potential Role of Alternative mRNA Splicing Events in Cervical Cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…SRSF3, as a potential diagnostic and prognostic biomarker, is upregulated in multiple types of human cancer, including breast cancer ( 85 – 88 ), ovarian cancer ( 26 , 89 ), retinoblastoma ( 90 , 91 ), head and neck cell squamous ( 62 , 79 , 92 ), glioblastoma (GBM) ( 23 ), gastric cancer ( 36 ), colorectal cancer (CRC) ( 33 , 36 , 93 ), cervical cancer ( 94 ), and hepatocellular carcinoma (HCC) ( 30 , 95 ). Moreover, studies show SRSF3 upregulation not only in epithelial cancers, but also in mesenchymal tumors, as Table 1 shows ( 11 ).…”

Section: Srsf3 In Cancermentioning

confidence: 99%

Emerging Roles of SRSF3 as a Therapeutic Target for Cancer

et al. 2020

View full text Add to dashboard Cite

Ser/Arg-rich (SR) proteins are RNA-binding proteins known as constitutive and alternative splicing (AS) regulators that regulate multiple aspects of the gene expression program. Ser/Arg-rich splicing factor 3 (SRSF3) is the smallest member of the SR protein family, and its level is controlled by multiple factors and involves complex mechanisms in eukaryote cells, whereas the aberrant expression of SRSF3 is associated with many human diseases, including cancer. Here, we review state-of-the-art research on SRSF3 in terms of its function, expression, and misregulation in human cancers. We emphasize the negative consequences of the overexpression of the SRSF3 oncogene in cancers, the pathways underlying SRSF3-mediated transformation, and implications of potential anticancer drugs by downregulation of SRSF3 expression for cancer therapy. Cumulative research on SRSF3 provides critical insight into its essential part in maintaining cellular processes, offering potential new targets for anti-cancer therapy.

show abstract

“…17 These data have established SFs as tumor biomarkers. 19,20 The expression level of hnRNPs has also been altered in many types of cancer, suggesting their role in tumorigenesis, as well as presenting functional versatility within the hnRNP family members. 21 Proteins from the hnRNP family can repress splicing by directly antagonizing the recognition of splice sites, interfering with the binding of proteins associated with enhancers or hindering communication between factors attached to different splice sites.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin-c isoform levels are associated with SR and hnRNP differential expression in ovarian cancer cell lines

et al. 2017

View full text Add to dashboard Cite

Osteopontin-c splicing isoform activates ovarian cancer progression features. Imbalanced expression of splicing factors from serine/arginine -rich and heterogeneous ribonucleoproteins families has been correlated with the generation of oncogenic splicing isoforms. Our goal was to investigate whether there is any association between the transcriptional patterns of these splicing factors in ovarian cells and osteopontin-c expression levels. We also aimed to investigate the occurrence of these splicing factors binding sites inside osteopontin exon 4 and adjacent introns. To test associations between osteopontin-c and splicing factors expression patterns, we used an in vitro model in which OVCAR-3 cells overexpressing osteopontin-c (OVCAR-3/OPNc) presented higher transcriptional levels of osteopontin-c than two other ovarian carcinoma cells (TOV-112D, SKOV-3) and ovarian non-tumoral cell lines (IOSE 364 and IOSE 385). The transcriptional levels of osteopontin-c, serine/arginine-rich, and hnRNP factors were evaluated using real-time polymerase chain reaction. Human Splice Finder software was used to search for putative splicing factor binding sites in osteopontin genomic regions. OVCAR-3/OPNc cells presented higher transcriptional levels of hnRNP than serine/arginine-rich when compared to TOV-112D, SKOV-3, and IOSE cells. TOV-112D and SKOV-3 cells also overexpressed hnRNP in relation to serine/arginine-rich transcripts. Putative binding sites for these splicing factors have been predicted on osteopontin exon 4 and their upstream and downstream intronic regions. Our data showed that higher osteopontin-c expression levels are associated with a predominance of hnRNP in relation to serine/arginine-rich transcripts and that osteopontin exon 4 and adjacent intronic sequences contain predicted binding sites for some of these tested splicing factors. In conclusion, differential expression of these splicing factors in ovarian cancer cells could be one of the putative mechanisms leading to aberrant splicing of the osteopontin primary transcript. Future work, aiming to control ovarian cancer progression by downregulating osteopontin-c levels, could include strategies that also regulate heterogeneous ribonucleoproteins and serine/arginine-rich expression levels in order to modulate osteopontin splicing.

show abstract

HNRNPA1, a Splicing Regulator, Is an Effective Target Protein for Cervical Cancer Detection: Comparison With Conventional Tumor Markers

Cited by 17 publications

References 22 publications

Prognostic Value and Potential Role of Alternative mRNA Splicing Events in Cervical Cancer

Prognostic Value and Potential Role of Alternative mRNA Splicing Events in Cervical Cancer

Emerging Roles of SRSF3 as a Therapeutic Target for Cancer

Osteopontin-c isoform levels are associated with SR and hnRNP differential expression in ovarian cancer cell lines

Contact Info

Product

Resources

About