High mobility group A protein-2 as a tumor cancer diagnostic and prognostic marker: a systematic review and meta-analysis

Pham, Yen Thi-Hai; Utuama, Ovie; Thomas, Catherine A.; Park, Jong A.; Vecchia, Carlo La; Risch, Harvey A.; Tran, Chi Thi-Du; Le, Thanh Van; Boffetta, Paolo; Raskin, Leon; Luu, Hung N.

doi:10.1097/cej.0000000000000602

Cited by 4 publications

(1 citation statement)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Typical aberrations in HMGA2 function in cancer are due to overexpression, gene fusion, mutations or truncation (Fusco and Fedele, 2007; Hisaoka et al, 2002; Liu et al, 2020; Young and Narita, 2007). Aberrant HMGA2 re-expression is associated with poor tumor prognosis (Gundlach et al, 2021; Li et al, 2020; Strell et al, 2017; Thi-Hai Pham et al, 2020) and therapy resistance (Dangi-Garimella et al, 2011; Dangi-Garimella et al, 2013; Huldani et al, 2022). Functional studies demonstrated the role of HMGA2 in various aspects of neoplastic transformation (Fedele et al, 2006; Vallone et al, 1997), invasion (Thuault et al, 2006; Watanabe et al, 2009) and metastasis (Wang et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Up-regulated transcriptional regulators in mutant RAS gene signatures: a time-resolved multi-omics study in generic epithelial cell models

Kasack,

Metzger,

Koch

et al. 2024

Preprint

View full text Add to dashboard Cite

The expression of mutated RAS genes drives extensive transcriptome alterations. Perturbation experiments have shown that the transcriptional responses to downstream effector pathways are partially unique and non-overlapping, suggesting a modular organization of the RAS-driven expression program. However, the relationship between individual deregulated transcription factors and the entire cancer cell-specific genetic program is poorly understood. To identify potential regulators of the RAS/MAPK-dependent fraction of the genetic program, we monitored transcriptome and proteome changes following conditional, time-resolved expression of mutant HRASG12Vin human epithelial cells during neoplastic conversion. High mobility group AT hook2 (HMGA2), an architectural chromatin modulating protein and oncofetal tumour marker, was recovered as the earliest upregulated transcription factor. Knock-down of HMGA2 reverted anchorage-independent growth and epithelial-mesenchymal transition not only in HRAS-transformed cells but also in an independent, KRASG12V-driven rat epithelial model. Moreover, HMGA2 silencing reverted the deregulated expression of 60% of RAS-responsive target genes. These features qualify HMGA2 as a master regulator of mutant RAS-driven expression patterns. The delayed deregulation of FOSL1, ZEB1 and other transcription factors with known oncogenic activity suggests that HMGA2 acts in concert with a network of regulatory factors to trigger full neoplastic conversion. Although transcription factors are considered difficult to drug, the central role of HMGA2 in the transcription factor network as well as its relevance for cancer prognosis has motivated attempts to block its function using small molecular weight compounds. The further development of direct HMGA2 antagonists may prove useful in cancer cells that have developed resistance to signalling chain inhibition.

show abstract

Section: Discussionmentioning

confidence: 99%

Up-regulated transcriptional regulators in mutant RAS gene signatures: a time-resolved multi-omics study in generic epithelial cell models

Kasack,

Metzger,

Koch

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Decoding high mobility group A2 protein expression regulation and implications in human cancers

Khazem,

Zetoune

2024

Discov Onc

View full text Add to dashboard Cite

High Mobility Group A2 (HMGA2) oncofetal proteins are a distinct category of Transcription Factors (TFs) known as “architectural factors” due to their lack of direct transcriptional activity. Instead, they modulate the three-dimensional structure of chromatin by binding to AT-rich regions in the minor grooves of DNA through their AT-hooks. This binding allows HMGA2 to interact with other proteins and different regions of DNA, thereby regulating the expression of numerous genes involved in carcinogenesis. Consequently, multiple mechanisms exist to finely control HMGA2 protein expression at various transcriptional levels, ensuring precise concentration adjustments to maintain cellular homeostasis. During embryonic development, HMGA2 protein is highly expressed but becomes absent in adult tissues. However, recent studies have revealed its re-elevation in various cancer types. Extensive research has demonstrated the involvement of HMGA2 protein in carcinogenesis at multiple levels. It intervenes in crucial processes such as cell cycle regulation, apoptosis, angiogenesis, epithelial-to-mesenchymal transition, cancer cell stemness, and DNA damage repair mechanisms, ultimately promoting cancer cell survival. This comprehensive review provides insights into the HMGA2 protein, spanning from the genetic regulation to functional protein behavior. It highlights the significant mechanisms governing HMGA2 gene expression and elucidates the molecular roles of HMGA2 in the carcinogenesis process. Graphical Abstract

show abstract

Expression patterns ofHMGA2in the placenta during pregnancy

Burchardt

Gottlieb

Helmke

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundHigh-mobility group AT-hook 2 (HMGA2) expression can be detected in many embryonic and fetal tissues but becomes down-regulated during postnatal life except for many benign and malignant tumors. In the latter case, its expression has been correlated with epithelial-mesenchymal transition and invasive growth. The placenta contributes essentially to proper development of the embryo and the fetus. In a tumor-like manner it shows rapid invasive growth during the first weeks of gestation. To address the possible role of HMGA2 during placental development, we have measured its expression throughout the prenatal period and in term placentae by mRNA quantification as well as by immunohistochemistry.MethodsExpression of HMGA2 and HPRT was measured on 89 fetal placentas, encompassing calendar gestational age of five to 41 weeks, using quantitative real time-PCR. In eleven cases in addition immunohistochemistry was used to determine the localization of HMGA2 and to compare with data obtained by quantitative real time-PCR.ResultsThe expression of HMGA2 was found to be inversely correlated with gestational age (p < 0.001). For the first part of the first trimester the level of HMGA2 is high. After that the expression shows a decline down to a baseline level where it remains until birth. HMGA2 protein was mainly detected in the nuclei of the stromal cells in the placental villi.ConclusionsDuring pregnancy, the expression of HMGA2 follows a non-linear pattern of decrease. In the first trimester, from two to three weeks after the implantation of the conceptus until the blood supply is established (hypoxic phase), the expression is high, indicating a critical role during early development and in the control of its invasive behavior, respectively.

show abstract

High mobility group A protein-2 as a tumor cancer diagnostic and prognostic marker: a systematic review and meta-analysis

Cited by 4 publications

References 71 publications

Up-regulated transcriptional regulators in mutant RAS gene signatures: a time-resolved multi-omics study in generic epithelial cell models

Up-regulated transcriptional regulators in mutant RAS gene signatures: a time-resolved multi-omics study in generic epithelial cell models

Decoding high mobility group A2 protein expression regulation and implications in human cancers

Expression patterns ofHMGA2in the placenta during pregnancy

Contact Info

Product

Resources

About