PEG10 as an oncogene: expression regulatory mechanisms and role in tumor progression

Abstract

Cancer is a major public health problem as one of the leading causes of death worldwide. Deciphering the molecular regulation mechanisms of tumor progression can make way for tumor diagnosis and therapy. Paternally expressed gene 10 (PEG10), located on human chromosome 7q21.3, has turned out to be an oncogene implicated in the proliferation, apoptosis and metastasis of tumors. PEG10 has been found to be positively expressed in a variety of cancers with seemingly complex expression regulation mechanisms. In this review, we focus on the most vital factors influencing PEG10 expression and recapitulate some of the currently known and potential mechanisms of PEG10 affecting tumor progression, as understanding the molecular regulatory mechanisms of tumor progression can provide potential PEG10 related diagnosis and biomarker specific targeted therapies.

DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma

“…PEG10 plays a vital role in placental formation and differentiation of adipocytes while SGCE gene encodes a transmembrane protein that links the actin cytoskeleton to extracellular matrix 23 . However, deregulated PEG10 expression is associated with malignant transformation, affecting cell proliferation and apoptosis 24 . Both PEG10 and SGCE are known to be overexpressed in high-risk B-cell chronic lymphocytic leukemia (B-CLL), with promoter DNA methylation regulating the gene expression 24 .…”

“…However, deregulated PEG10 expression is associated with malignant transformation, affecting cell proliferation and apoptosis 24 . Both PEG10 and SGCE are known to be overexpressed in high-risk B-cell chronic lymphocytic leukemia (B-CLL), with promoter DNA methylation regulating the gene expression 24 . Overexpression of PEG10 has also been implicated in progression of various solid cancers including hepatocellular carcinoma 25 , pancreatic cancer 26 , breast cancer 27 and prostate cancer 24 .…”

“…Both PEG10 and SGCE are known to be overexpressed in high-risk B-cell chronic lymphocytic leukemia (B-CLL), with promoter DNA methylation regulating the gene expression 24 . Overexpression of PEG10 has also been implicated in progression of various solid cancers including hepatocellular carcinoma 25 , pancreatic cancer 26 , breast cancer 27 and prostate cancer 24 . Overexpression of PEG10 in these solid tumors was shown to correlate with higher TNM stage and lymph node metastasis 28 .…”

“…Interestingly, long non-coding RNA PEG10, also encoded from 7q21, was shown upregulated in diffuse large B cell lymphoma (DLBCL), which correlated with worse prognosis 29 . One of the oncogenic effects of PEG10 in the solid cancers has been shown to promote metastatic migration and promoting epithelial-mesenchymal transition of neoplastic cells 24 . The overlapping epigenetic and transcriptomic disparities identified between T-ALL and T-LBL in our study might contribute to the different manifestations of the malignancies.…”

Epigenetic aberrations in human pluripotent stem cells

“…Biallelic activation of an imprinted gene is expected to cause a twofold increase in its expression, but while some genes follow this simple linear model, others are transcribed at higher ( RTL1 , IGF2 ) or lower ( PEG10 , SGCE , NDN ) levels than anticipated, indicative of a more complex regulatory network (Bar et al , ). Correspondingly, upregulations of several imprinted genes, especially those with high rates of LOI in hESCs (e.g., IGF2 , PEG10 , DLK1 ), were implicated in various malignancies (Huang et al , ; Xu et al , ; Li et al , ; Brouwer‐Visser & Huang, ; Xie et al , ). Moreover, LOI is known to be highly frequent in many types of cancers, though accumulative evidence suggests it appears early and originates in the stem cell niche of the tissue which sourced the tumor.…”