The long non-coding RNA PTTG3P promotes growth and metastasis of cervical cancer through PTTG1

Guo, Xiangcui; Li, Li; Gao, Zhihui; Zhou, Hongwei; Li, Jun; Wang, Qianqing

doi:10.18632/aging.101830

Cited by 26 publications

(25 citation statements)

References 35 publications

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“…Nevertheless, an increasing number of research have demonstrated that pseudogenes can control functional genes through various mechanisms, thus regulating diverse physiological and pathological processes, including carcinogenesis ( 16 , 51 ). Previous studies reported many tumor-related pseudogenes such as PTENP1 ( 53 , 54 ), DUXAP10 ( 55 ), SUMO1P3 ( 56 ), PDIA3P ( 57 ), PTTG3P ( 24 ), and DUXAP8 ( 58 ). In the present study, we first identified 632 differentially expressed pseudogenes in BC based on data from the dreamBase database.…”

Section: Discussionmentioning

confidence: 99%

Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer

et al. 2020

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Immune checkpoint inhibitors (ICIs) have been successfully used for treating melanoma and non-small cell lung cancer. However, many patients with breast cancer (BC) show low response to ICIs due to the paucity of infiltrating immune cells. Pseudogenes, as a particular kind of long-chain noncoding RNA, play vital roles in tumorigenesis, but their potential roles in tumor immunology remain unclear. In this study that used data from online databases, the novel pseudogene HLA-DPB2 and its parental gene HLA-DPB1 were overexpressed and correlated with better prognosis in BC. Mechanistically, our results revealed that HLA-DPB2 might serve as an endogenous RNA to increase HLA-DPB1 expression by competitively binding with has-miR-370-3p . Functionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the HLA-DPB2/HLA-DPB1 axis was strongly relevant to immune-related biological functions. Further analysis demonstrated that high expression levels of the HLA-DPB2 and HLA-DPB1 were significantly associated with high immune infiltration abundance of CD8+ T cells, CD4+ T cells, Tfh, Th1, and NK cells and with high expression of majority biomarkers of monocytes, NK cell, T cell, CD8+ T cell, and Th1 in BC and its subtype, indicating that HLA-DPB2 can increase the abundance of tumor-infiltrating lymphocytes in the BC microenvironment. Also, the HLA-DPB2 and HLA-DPB1 expression levels positively correlated with the expression levels of programmed cell death protein 1, programmed cell death ligand 1, and cytotoxic T-lymphocyte-associated antigen-4. Our findings suggest that pseudogene HLA-DPB2 can upregulate HLA-DPB1 through sponging has-miR-370-3p, thus exerting its antitumor effect by recruiting tumor-infiltrating immune cells into the breast tumor microenvironment, and that targeting the HLA-DPB2/HLA-DPB1 axis with ICIs may optimize the current immunotherapy for BC.

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Section: Discussionmentioning

confidence: 99%

Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer

et al. 2020

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“…The PTTG gene family consists of three members: one pseudogene ( PTTG3P ) and two protein coding genes, namely PTTG1 and PTTG2 [ 12 ]. Numerous studies have proven the significant role of PTTGs in cancer initiation and progression [ 11 , 13 , 16 , 17 , 18 ], although the mechanisms of these processes mostly remain unclear. It is known that PTTG3P influences tumor growth and metastasis in both cervical cancer and hepatocellular carcinoma [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have proven the significant role of PTTGs in cancer initiation and progression [ 11 , 13 , 16 , 17 , 18 ], although the mechanisms of these processes mostly remain unclear. It is known that PTTG3P influences tumor growth and metastasis in both cervical cancer and hepatocellular carcinoma [ 17 , 18 ]. Similarly, the second member, PTTG1 , has been reported to promote migration and invasion in non-small cell lung cancer [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it has a limited protein-coding capacity, and thus, it is regarded as one long non-coding RNA (lncRNA). The mechanisms of PTTG3P functions are not yet well understood, but it has been demonstrated that PTTG3P promotes both proliferation and invasion throght upregulation of PTTG1 and is an indicator of bad prognosis in cervical cancer and hepatocellular carcinoma [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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The Oncogenic Roles of PTTG1 and PTTG2 Genes and Pseudogene PTTG3P in Head and Neck Squamous Cell Carcinomas

et al. 2020

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Background: Head and neck squamous cell carcinomas are a group of heterogeneous diseases that occur in the mouth, pharynx and larynx and are characterized by poor prognosis. A low overall survival rate leads to a need to develop biomarkers for early head and neck squamous cell carcinomas detection, accurate prognosis and appropriate selection of therapy. Therefore, in this paper, we investigate the biological role of the PTTG3P pseudogene and associated genes PTTG1 and PTTG2 and their potential use as biomarkers. Methods: Based on TCGA data and the UALCAN database, PTTG3P, PTTG1 and PTTG2 expression profiles and clinicopathological features with TP53 gene status as well as expression levels of correlated genes were analyzed in patients’ tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. Gene Set Enrichment Analysis software was used for functional enrichment analysis. All statistical analyses were performed using GraphPad Prism 5. Results: In head and neck squamous cell carcinomas, significant up-regulation of the PTTG3P pseudogene, PTTG1 and PTTG2 genes’ expression between normal and cancer samples were observed. Moreover, the expression of PTTG3P, PTTG1 and PTTG2 depends on the type of mutation in TP53 gene, and they correlate with genes from p53 pathway. PTTG3P expression was significantly correlated with PTTG1 as well as PTTG2, as was PTTG1 expression with PTTG2. Significant differences between expression levels of PTTG3P, PTTG1 and PTTG2 in head and neck squamous cell carcinomas patients were also observed in clinicopathological contexts. The contexts taken into consideration included: T-stage for PTTG3P; grade for PTTG3, PTTG1 and PTTG2; perineural invasion and lymph node neck dissection for PTTG1 and HPV p16 status for PTTG3P, PTTG1 and PTTG2. A significantly longer disease-free survival for patients with low expressions of PTTG3P and PTTG2, as compared to high expression groups, was also observed. Gene Set Enrichment Analysis indicated that the PTTG3 high-expressing group of patients have the most deregulated genes connected with DNA repair, oxidative phosphorylation and peroxisome pathways. For PTTG1, altered genes are from DNA repair groups, Myc targets, E2F targets and oxidative phosphorylation pathways, while for PTTG2, changes in E2F targets, G2M checkpoints and oxidative phosphorylation pathways are indicated. Conclusions: PTTG3P and PTTG2 can be used as a prognostic biomarker in head and neck squamous cell carcinomas diagnostics. Moreover, patients with high expressions of PTTG3P, PTTG1 or PTTG2 have worse outcomes due to upregulation of oncogenic pathways and more aggressive phenotypes.

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“…Cervical cancer is one of the most common gynecological malignancies (57). The pathogenesis of cervical cancer is a complex process involving multiple factors and steps (58,59). It is therefore important to search for molecular markers and therapeutic targets for the treatment of cervical cancer.…”

Section: Txnip and Cervical Cancermentioning

confidence: 99%

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

et al. 2020

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Thioredoxin-interacting protein (TXNIP) is a thioredoxin-binding protein that can mediate oxidative stress, inhibit cell proliferation, and induce apoptosis by inhibiting the function of the thioredoxin system. TXNIP is important because of its wide range of functions in cardiovascular diseases, neurodegenerative diseases, cancer, diabetes, and other diseases. Increasing evidence has shown that TXNIP expression is low in tumors and that it may act as a tumor suppressor in various cancer types such as hepatocarcinoma, breast cancer, and lung cancer. TXNIP is known to inhibit the proliferation of breast cancer cells by affecting metabolic reprogramming and can affect the invasion and migration of breast cancer cells through the TXNIP-HIF1α-TWIST signaling axis. TXNIP can also prevent the occurrence of bladder cancer by inhibiting the activation of ERK, which inhibits apoptosis in bladder cancer cells. In this review, we find that TXNIP can be regulated by binding to transcription factors or other binding proteins and can also be downregulated by epigenetic changes or miRNA. In addition, we also summarize emerging insights on TXNIP expression and its functional role in different kinds of cancers, as well as clarify its participation in metabolic reprogramming and oxidative stress in cancer cells, wherein it acts as a putative tumor suppressor gene to inhibit the proliferation, invasion, and migration of different tumor cells as well as promote apoptosis in these cells. TXNIP may therefore be of basic and clinical significance for finding novel molecular targets that can facilitate the diagnosis and treatment of malignant tumors.

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The long non-coding RNA PTTG3P promotes growth and metastasis of cervical cancer through PTTG1

Cited by 26 publications

References 35 publications

Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer

Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer

The Oncogenic Roles of PTTG1 and PTTG2 Genes and Pseudogene PTTG3P in Head and Neck Squamous Cell Carcinomas

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

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