CDKN3 mRNA as a Biomarker for Survival and Therapeutic Target in Cervical Cancer

Barrón, Eira Valeria; Román-Bassaure, Edgar; Sánchez-Sandoval, Ana Laura; Espinosa, Ana; Guardado-Estrada, Mariano; Medina, Ingrid; Juárez, Eligia; Alfaro, Ana; Bermúdez, Miriam; Zamora, Rubén; García-Ruiz, Carlos; Gómora, Juan Carlos; Kofman, Susana; Pérez-Armendáriz, E. Martha; Berumen, Jaime

doi:10.1371/journal.pone.0137397

Cited by 34 publications

(24 citation statements)

References 60 publications

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“…An exon 2-skipping alternative splicing transcript (Fig. 1) was consistently detected in both normal and tumor cells and tissues (Barron et al, 2015; Fan et al, 2015; Yu et al, 2007). …”

Section: Cdkn3mentioning

confidence: 94%

“…1). In addition to this 212-amino acid residue encoding CDKN3 transcript, several splicing variants have been reported (Barron et al, 2015; Fan et al, 2015; Yeh et al, 2000; Yu et al, 2007). An exon 2-skipping alternative splicing transcript (Fig.…”

Section: Cdkn3mentioning

confidence: 99%

“…Subsequently, increased CDKN3 expression has been observed in many types of cancer (Fan et al, 2015; Yang and Sun, 2015). Moreover, high CDKN3 mRNA levels have been associated with poor survival in glioma (Yu et al, 2007), cervical cancer (Barron et al, 2015; Espinosa et al, 2013), and lung adenocarcinoma (Fan et al, 2015; Zang et al, 2015). Examination of The Cancer Genome Atlas (TCGA) RNA-seq data (via cBioPortal) also indicates that high CDKN3 mRNA levels correlate with poor survival in several types of cancer, including renal clear cell carcinoma, renal papillary cell carcinoma, low grade glioma, and prostate adenocarcinoma (see below).…”

Section: Cdkn3 Overexpression Is Associated With Poor Survival In mentioning

confidence: 99%

“…In addition, an exon 2-skip alternative splicing isoform is present in all human cell lines and tissues that have been analyzed (Barron et al, 2015; Fan et al, 2015; Yu et al, 2007). The exon 2-skip transcript results in a frameshift and encodes a short 23-amino acid residue peptide non-homologous to CDKN3.…”

Section: Normal and Aberrant Cdkn3 Transcriptsmentioning

confidence: 99%

“…Barron et al (Barron et al, 2015) reported five minor aberrant transcripts in cervical cancer and control tissues. These transcripts were generated from alternative splicing lacking internal exons or distal exons, but retaining exons 4, 6, 7, and/or 8 that encode CDK2 interacting regions of CDKN3 (Song et al, 2001).…”

Section: Normal and Aberrant Cdkn3 Transcriptsmentioning

confidence: 99%

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Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3 gene in human cancer

Cress

2017

The International Journal of Biochemistry & Cell Biology

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The cyclin-dependent kinase inhibitor-3 (CDKN3) gene encodes a dual-specificity protein tyrosine phosphatase that dephosphorylates CDK1/CDK2 and other proteins. CDKN3 is often overexpressed in human cancer, and this overexpression correlates with reduced survival in several types of cancer. CDKN3 transcript variants and mutations have also been reported. The mechanism of CDKN3 overexpression and the role of CDKN3 transcript variants in human cancer are not entirely clear. Here, we review the literature and provide additional data to assess the correlation of CDKN3 expression with patient survival. Besides the full-length CDKN3 encoding transcript and a major transcript that skips exon 2 express in normal and cancer cells, minor aberrant transcript variants have been reported. Aberrant CDKN3 transcripts were postulated to encode dominant-negative inhibitors of CDKN3 as an explanation for overexpression of the perceived tumor suppressor gene in human cancer. However, while CDKN3 is often overexpressed in human cancer, aberrant CDKN3 transcripts occur infrequently and at lower levels. CDKN3 mutations and copy number alternation are rare in human cancer, implying that neither loss of CDKN3 activity nor constitutive gain of CDKN3 expression offer an advantage to tumorigenesis. Recently, it was found that CDKN3 transcript and protein levels fluctuate during the cell cycle, peaking in mitosis. Given that rapidly growing tumors have more mitotic cells, the high level of mitotic CDKN3 expression is the most plausible mechanism of frequent CDKN3 overexpression in human cancer. This finding clarifies the mechanism of CDKN3 overexpression in human cancer and questions the view of CDKN3 as a tumor suppressor.

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“…An exon 2-skipping alternative splicing transcript (Fig. 1) was consistently detected in both normal and tumor cells and tissues (Barron et al, 2015; Fan et al, 2015; Yu et al, 2007). …”

Section: Cdkn3mentioning

confidence: 94%

Section: Cdkn3mentioning

confidence: 99%

Section: Cdkn3 Overexpression Is Associated With Poor Survival In mentioning

confidence: 99%

Section: Normal and Aberrant Cdkn3 Transcriptsmentioning

confidence: 99%

Section: Normal and Aberrant Cdkn3 Transcriptsmentioning

confidence: 99%

See 3 more Smart Citations

Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3 gene in human cancer

Cress

2017

The International Journal of Biochemistry & Cell Biology

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Genetic Testing in Cervical Cancer

Sharma,

Singh

2023

Genetic Testing in Reproductive Medicine

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An anoikis-based gene signature for predicting prognosis in malignant pleural mesothelioma and revealing immune infiltration

Shi

Peng

Zhang

et al. 2023

J Cancer Res Clin Oncol

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Introduction: Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant tumor. Anoikis is a particular type of programmed apoptosis brought on by the separation of cell-cell or extracellular matrix (ECM). Anoikis has been recognized as a crucial element in the development of tumors. However, few studies have comprehensively examined the role of anoikis-related genes (ARGs) in malignant mesothelioma.Methods: ARGs were gathered from the GeneCard database and the Harmonizome portals. We obtained differentially expressed genes (DEGs) using the GEO database. Univariate Cox regression analysis, and the least absolute shrinkage and selection operator (LASSO) algorithm were utilized to select ARGs associated with the prognosis of MPM. We then developed a risk model, and time-dependent receiver operating characteristic (ROC) analysis and calibration curves were employed to con rm the ability of the model. The patients were divided into various subgroups using consensus clustering analysis. Based on the median risk score, patients were divided into low-and high-risk groups. Functional analysis and immune cell in ltration analysis were conducted to estimate molecular mechanisms and the immune in ltration landscape of patients. Lastly, drug sensitivity analysis and tumor microenvironment landscape were further explored.Results: A novel risk model was constructed based on the six ARGs. The patients were successfully divided into two subgroups by consensus clustering analysis, with a striking difference in the prognosis and landscape of immune in ltration. The Kaplan-Meier survival analysis indicated that the OS rate of the low-risk group was signi cantly higher than the high-risk group. Functional analysis, immune cell in ltration analysis, and drug sensitivity analysis showed that high-and low-risk groups had different immune statuses and drug sensitivity.Conclusions: In summary, we developed a novel risk model to predict MPM prognosis based on six selected ARGs, which could broaden comprehension of personalized and precise therapy approaches for MPM.

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CDKN3 mRNA as a Biomarker for Survival and Therapeutic Target in Cervical Cancer

Cited by 34 publications

References 60 publications

Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3 gene in human cancer

Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3 gene in human cancer

Genetic Testing in Cervical Cancer

An anoikis-based gene signature for predicting prognosis in malignant pleural mesothelioma and revealing immune infiltration

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