High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer

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Abstract

Pseudogenes play pivotal roles in tumorigenesis. Previous studies have suggested that pituitary tumor-transforming 3, pseudogene (PTTG3P), serves as an oncogene in human cancers. However, its expression pattern, biological function , and underlying mechanism in breast cancer remain unknown. In this study, we demonstrated an elevated expression of PTTG3P in breast cancer and discovered that PTTG3P expression correlated negatively with estrogen receptor (ER) and progesterone receptor (PR) status, but linked positively to basal-like status, triple-negative breast cancer status, Nottingham prognostic index (NPI) , and Scarff-Bloom-Richardson grade. High expression of PTTG3P was also found to be associated with a poor prognosis of breast cancer. To explore the potential mechanisms of PTTG3P, a PTTG3P-microRNA (miRNA)-mRNA regulatory network was established. Co-expressed genes of PTTG3P were also obtained. Enrichment analysis for these co-expressed genes revealed that they were significantly enriched in mitotic nuclear division and cell cycle. Subsequent research on mechanism of PTTG3P indicated that its expression correlated positively with PTTG1 expression. However, no significant expression correlation between PTTG3P and PTTG2 was observed. Taken together, our findings suggest that increased expression of pseudogene PTTG3P may be used as a promising prognostic biomarker and novel therapeutic target for breast cancer.

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bc-GenExMiner: an easy-to-use online platform for gene prognostic analyses in breast cancer.

Pascal Jézéquel, Mario Campone, Wilfried Gouraud … (2012)

Gene prognostic meta-analyses should benefit from breast tumour genomic data obtained during the last decade. The aim was to develop a user-friendly, web-based application, based on DNA microarrays results, called "breast cancer Gene-Expression Miner" (bc-GenExMiner) to improve gene prognostic analysis performance by using the same bioinformatics process. bc-GenExMiner was developed as a web-based tool including a MySQL relational database. Survival analyses are performed with R statistical software and packages. Molecular subtyping was performed by means of three single sample predictors (SSPs) and three subtype clustering models (SCMs). Twenty-one public data sets have been included. Among the 3,414 recovered breast cancer patients, 1,209 experienced a pejorative event. Molecular subtyping by means of three SSPs and three SCMs was performed for 3,063 patients. Furthermore, three robust lists of stable subtyped patients were built to maximize reliability of molecular assignment. Gene prognostic analyses are done by means of univariate Cox proportional hazards model and may be conducted on cohorts split by nodal (N), oestrogen receptor (ER), or molecular subtype status. To evaluate independent prognostic impact of genes relative to Nottingham Prognostic Index and Adjuvant! Online, adjusted Cox proportional hazards models are performed. bc-GenExMiner allows researchers without specific computation skills to easily and quickly evaluate the in vivo prognostic role of genes in breast cancer by means of Cox proportional hazards model on large pooled cohorts, which may be split according to different prognostic parameters: N, ER, and molecular subtype. Prognostic analyses by molecular subtype may also be performed in three robust molecular subtype classifications.

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Foxo3 activity promoted by non-coding effects of circular RNA and Foxo3 pseudogene in the inhibition of tumor growth and angiogenesis.

W. P. Yang, W W Du, X-X Li … (2016)

It has recently been shown that the upregulation of a pseudogene specific to a protein-coding gene could function as a sponge to bind multiple potential targeting microRNAs (miRNAs), resulting in increased gene expression. Similarly, it was recently demonstrated that circular RNAs can function as sponges for miRNAs, and could upregulate expression of mRNAs containing an identical sequence. Furthermore, some mRNAs are now known to not only translate protein, but also function to sponge miRNA binding, facilitating gene expression. Collectively, these appear to be effective mechanisms to ensure gene expression and protein activity. Here we show that expression of a member of the forkhead family of transcription factors, Foxo3, is regulated by the Foxo3 pseudogene (Foxo3P), and Foxo3 circular RNA, both of which bind to eight miRNAs. We found that the ectopic expression of the Foxo3P, Foxo3 circular RNA and Foxo3 mRNA could all suppress tumor growth and cancer cell proliferation and survival. Our results showed that at least three mechanisms are used to ensure protein translation of Foxo3, which reflects an essential role of Foxo3 and its corresponding non-coding RNAs.

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bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses

Pascal Jézéquel, Jean-Sébastien Frénel, Loïc Campion … (2013)

We recently developed a user-friendly web-based application called bc-GenExMiner (http://bcgenex.centregauducheau.fr), which offered the possibility to evaluate prognostic informativity of genes in breast cancer by means of a ‘prognostic module’. In this study, we develop a new module called ‘correlation module’, which includes three kinds of gene expression correlation analyses. The first one computes correlation coefficient between 2 or more (up to 10) chosen genes. The second one produces two lists of genes that are most correlated (positively and negatively) to a ‘tested’ gene. A gene ontology (GO) mining function is also proposed to explore GO ‘biological process’, ‘molecular function’ and ‘cellular component’ terms enrichment for the output lists of most correlated genes. The third one explores gene expression correlation between the 15 telomeric and 15 centromeric genes surrounding a ‘tested’ gene. These correlation analyses can be performed in different groups of patients: all patients (without any subtyping), in molecular subtypes (basal-like, HER2+, luminal A and luminal B) and according to oestrogen receptor status. Validation tests based on published data showed that these automatized analyses lead to results consistent with studies’ conclusions. In brief, this new module has been developed to help basic researchers explore molecular mechanisms of breast cancer. Database URL: http://bcgenex.centregauducheau.fr

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Author and article information

Contributors

Weiyang Lou

Weimin Fan

Journal

Journal ID (nlm-ta): Mol Ther Oncolytics

Journal ID (iso-abbrev): Mol Ther Oncolytics

Title: Molecular Therapy Oncolytics

Publisher: American Society of Gene & Cell Therapy

ISSN (Electronic): 2372-7705

Publication date PMC-release: 27 March 2019

Publication date Collection: 27 September 2019

Publication date (Electronic): 27 March 2019

Volume: 14

Pages: 15-26

Affiliations

[1 ]Program of Innovative Cancer Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China

[2 ]Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310003, China

[3 ]Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310000, China

[4 ]Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA

Author notes

[∗ ]Corresponding author: Weiyang Lou, Program of Innovative Cancer Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. 11718264@ 123456zju.edu.cn

[∗∗ ]Corresponding author: Weimin Fan, Program of Innovative Cancer Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. fanw@ 123456zju.edu.cn

Article

Publisher ID: S2372-7705(19)30036-1

DOI: 10.1016/j.omto.2019.03.006

PMC ID: 6463746

SO-VID: 750963cd-7a7e-41fd-b9a1-db22e4616bef

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

History

Date received : 1 December 2018

Date accepted : 13 March 2019

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High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer

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Most cited references 33

bc-GenExMiner: an easy-to-use online platform for gene prognostic analyses in breast cancer.

Foxo3 activity promoted by non-coding effects of circular RNA and Foxo3 pseudogene in the inhibition of tumor growth and angiogenesis.

bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses

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