HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous RNA mechanism

Martino, Marco De; Forzati, Floriana; Marfella, Marianna; Pellecchia, Simona; Arra, Claudio; Terracciano, Luigi; Esposito, Francesco

doi:10.1038/srep37622

Cited by 35 publications

(50 citation statements)

References 44 publications

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“…Intriguingly, it has been demonstrated that pseudogenes’ regulation upon target gene expression is sometimes more than functioning through their cognate genes. For instance, pseudogene‐HMGA1P7 can regulate the expression of H19 and IGF2 as well as its cognate gene‐HMGA1 . In the present study, we found that overexpression of PTENP1 resulted in the upregulation of SOCS6 expression in both mRNA and protein levels.…”

Section: Discussionsupporting

confidence: 56%

“…Therefore, we investigated possible candidate targets of PTENP1 using starBase v2.0. We found several downstream moleculars, including SOCS6, RUNX3, Smad4, Smad5, FOXO1, and KLF4 . The expression of these targets in Eca109 and TE‐1 cells was evaluated by qRT‐PCR.…”

Section: Resultsmentioning

confidence: 99%

“…PTENP1, especially its 3′UTR, was previously reported to be a competing endogenous RNA (ceRNA) of PTEN . By functioning as a miRNAs’ decoy, pseudogenes like HMGA1 or PTENP1 were capable of upregulating multiple targets with tumor suppressive activities . Such effect of PTENP1 may protect SOCS6 transcripts from microRNA‐mediated downregulation at post‐transcriptional level …”

Section: Resultsmentioning

confidence: 99%

“…PTENP1, especially its 3′untranslated regions (3′UTR), acts as a competing endogenous RNA (ceRNA) that protects PTEN transcripts from microRNA‐mediated downregulation at post‐transcriptional level in several cancers, such as colon carcinoma and prostate cancer . In addition, similar to that HMGA1 pseudogene (HMGA1Ps) regulates the expression of HMGA2, IGF2, and H19, PTENP1 is also capable of upregulating lots of other targets with tumor suppressive activities by functioning as a miRNAs’ decoy . Furthermore, Gao et al found that expression of PTENP1 in oral squamous cell carcinoma tissues was negatively associated with patients prognosis .…”

Section: Introductionmentioning

confidence: 99%

“…13 In addition, similar to that HMGA1 pseudogene (HMGA1Ps) regulates the expression of HMGA2, IGF2, and H19, PTENP1 is also capable of upregulating lots of other targets with tumor suppressive activities by functioning as a miRNAs' decoy. 13,14 Furthermore, Gao et al found that expression of PTENP1 in oral squamous cell carcinoma tissues was negatively associated with patients prognosis. 15 Circulating PTENP1 in sera contributed to maintaining surveillance and forecast prognosis for patients with ccRCC or gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

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PTENP1 inhibits the growth of esophageal squamous cell carcinoma by regulating SOCS6 expression and correlates with disease prognosis

Gong

Zheng

Huang

et al. 2017

Molecular Carcinogenesis

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PTEN pseudogene (PTENP1) has a tumor suppressive role in multiple cancers. However, its involvement in esophageal squamous cell carcinoma (ESCC) remains largely unknown. In this study, we set out to identify the role of PTENP1 in the development of ESCC. Gene Expression Omnibus database was employed to investigate the expression of PTENP1 in ESCC. sRNA target Database (StarBase v2.0) was used to query the downstream of PTENP1. Next, both in vitro and in vivo experiments were employed to explore the function. Cell proliferation was evaluated by CCK‐8, soft agar, and colony formation assays. Expression of relative genes was assessed by quantitative real‐time PCR (qRT‐PCR) and Western blotting. 3′UTR luciferase assay was used to confirm the miRNA binding. The clinical significance of PTENP1 was further validated by immunohistochemistry (IHC) and correlation with clinicopathological indicators in additional samples (n = 93). We found expression of PTENP1 in ESCC was lower than that in the corresponding adjacent normal tissues (n = 17). Overexpression of PTENP1 in Eca109 and TE‐1 cells resulted in inhibited proliferation and altered expression of SOCS6‐p‐STAT3‐HIF‐1α pathway both in vitro and in vivo. Subsequent IHC reported a similar trend in human ESCC samples. 3′UTR luciferase assay demonstrated that PTENP1 3′UTR decoyed miR‐17‐5p from binding to SOCS6. Moreover, PTENP1 expression was correlated with clinicopathological indicators to varying degrees, including histological grade, TNM stage, infiltration depth, lymph node metastasis, and overall survival. Taken together, these results suggested an anti‐oncogenic role of PTENP1. Meanwhile, PTENP1 may also serve as a candidate of prognostic indicator for ESCC patients.

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Section: Discussionsupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

PTENP1 inhibits the growth of esophageal squamous cell carcinoma by regulating SOCS6 expression and correlates with disease prognosis

Gong

Zheng

Huang

et al. 2017

Molecular Carcinogenesis

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Critical role of the high mobility group A proteins in hematological malignancies

Martino

Esposito

2021

Hematological Oncology

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The high mobility group A (HMGA) protein family is composed of three non-histone chromatin remodeling proteins that act as architectural transcriptional factors. Indeed, although HMGA proteins lack transcriptional activity per se, they bind the minor groove of DNA at AT-rich sequences, and, interacting with the transcription machinery, are able to modify chromatin modeling, thus regulating the expression of several genes. HMGA proteins have been deeply involved in embryogenesis process, and a large volume of studies has pointed out their key role in human cancer.Here, we review the studies on the role of the HMGA proteins in human hematological malignancies: they are overexpressed in most of the cases and their expression correlates with a reduced survival. In some cases, such as in acute lymphoblastic leukemia and acute myelogenous leukemia, HMGA2 gene rearrangements have been also described. Finally, recent studies evidence a synergism between HMGA and EZH2 in diffuse B-cell lymphomas, suggesting an innovative therapy for this disease based on the inhibition of the function of both these proteins.

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Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer

Abdollahzadeh

Daraei

Mansoori

et al. 2018

Journal Cellular Physiology

231

185

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Breast cancer (BC) is the most frequently occurring malignancy in women worldwide. Despite the substantial advancement in understanding the molecular mechanisms and management of BC, it remains the leading cause of cancer death in women. One of the main reasons for this obstacle is that we have not been able to find the Achilles heel for the BC as a highly heterogeneous disease. Accumulating evidence has revealed that noncoding RNAs (ncRNAs), play key roles in the development of BC; however, the involving of complex regulatory interactions between the different varieties of ncRNAs in the development of this cancer has been poorly understood. In the recent years, the newly discovered mechanism in the RNA world is “competing endogenous RNA (ceRNA)” which proposes regulatory dialogues between different RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). In the latest BC research, various studies have revealed that dysregulation of several ceRNA networks (ceRNETs) between these ncRNAs has fundamental roles in establishing the hallmarks of BC development. And it is thought that such a discovery could open a new window for a better understanding of the hidden aspects of breast tumors. Besides, it probably can provide new biomarkers and potential efficient therapeutic targets for BC. This review will discuss the existing body of knowledge regarding the key functions of ceRNETs and then highlights the emerging roles of some recently discovered ceRNETs in several hallmarks of BC. Moreover, we propose for the first time the “ceRnome” as a new term in the present article for RNA research.

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HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous RNA mechanism

Cited by 35 publications

References 44 publications

PTENP1 inhibits the growth of esophageal squamous cell carcinoma by regulating SOCS6 expression and correlates with disease prognosis

PTENP1 inhibits the growth of esophageal squamous cell carcinoma by regulating SOCS6 expression and correlates with disease prognosis

Critical role of the high mobility group A proteins in hematological malignancies

Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer

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