A Novel Splice Variant of the Inhibitor of Growth 3 Lacks the Plant Homeodomain and Regulates Epithelial–Mesenchymal Transition in Prostate Cancer Cells

Melekhova, Anna; Leeder, Mirjam; Pungsrinont, Thanakorn; Schmäche, Tim; Kallenbach, Julia; Ehsani, Marzieh; Mirzakhani, Kimia; Rasa, Seyed Mohammad Mahdi; Neri, Francesco; Baniahmad, Aria

doi:10.3390/biom11081152

Cited by 5 publications

(11 citation statements)

References 36 publications

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“…ING2, in turn, increased the levels of cell cycle inhibitor p16 and senescent PC cells [38]. Both ING3 up-and downregulation in PC cells resulted in cellular senescence induction through the upregulation of p21 expression [39]. This suggests that the ING3 protein levels in PC must be balanced in order to allow cancer cells to proliferate.…”

Section: Tumour Suppressive Pathways Of Ing Factorsmentioning

confidence: 99%

“…This suggests that the ING3 protein levels in PC must be balanced in order to allow cancer cells to proliferate. Notably, the expression of ING3 splice variants must also be taken into consideration since they may affect intracellular pathways in a distinct manner [39].…”

Section: Tumour Suppressive Pathways Of Ing Factorsmentioning

confidence: 99%

“…Some ING proteins were reported to hamper angiogenesis, migration, and invasion capacity of malignant cells [17,24,[40][41][42][43]. ING3 protects PC cells from metastasis-associated epithelial-mesenchymal transition (EMT) characterised by decreased protein expression of epithelial marker E-Cadherin and upregulated expression of mesenchymal markers N-Cadherin and Vimentin [39,44,45]. ING4 and ING5 possess high amino acid sequence homology and share inhibitory function on EMT that subsequently reduce migration and invasion capacity of malignant cells [18,[46][47][48][49][50].…”

Section: Ing Factors Regulate Emtmentioning

confidence: 99%

“…Besides mutations, splicing events may change the ING-factor activity. As an example, the lack of functional LZL domain disturbs ING2-induced apoptosis [68], or the splice variant ING3∆ex11 that lacks the PHD cannot prevent EMT induction in PC cells [39]. This is evidence that the splicing of exons from precursor RNA, which results in transcript variants encoding a different composition of functional domains, leads to ING isoforms with modified activity.…”

Section: The Role Of Ing Isoforms and Splice Variantsmentioning

confidence: 99%

“…ING3 was also reported to act isoform-specifically in PC. Recently, a novel ING3 splice variant ING3Δex11 was identified in both a human PC cell line and in human PC patientderived tissues [39]. This new splice variant counteracts the longest ING3 isoform.…”

Section: The Role Of Ing Isoforms and Splice Variantsmentioning

confidence: 99%

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ING Tumour Suppressors and ING Splice Variants as Coregulators of the Androgen Receptor Signalling in Prostate Cancer

Melekhova

Baniahmad

2021

Cells

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Prevention and overcoming castration resistance of prostate cancer (PC) remains one of the main unsolved problems in modern oncology. Hence, many studies are focused on the investigation of novel androgen receptor (AR) regulators that could serve as potential drug targets in disease therapy. Among such factors, inhibitor of growth (ING) proteins were identified. Some ING proteins act as AR transcriptional coregulators, indicating their relevance for PC research. The ING family consists of five protein-coding genes from ING1 to ING5 and pseudogene INGX. The ING genes were revealed through their sequence homology to the first identified ING1 from an in vivo screen. ING factors are a part of histone modification complexes. With the help of the conserved plant homeodomain (PHD) motif, ING factors bind to Histone 3 Lysine 4 (H3K4) methylation mark with a stronger affinity to the highest methylation grade H3K4me3 and recruit histone acetyltransferases (HAT) and histone deacetylases (HDAC) to chromatin. ING1 and ING2 are core subunits of mSIN3a-HDAC corepressor complexes, whereas ING3–5 interact with different HAT complexes that serve as coactivators. ING members belong to type II tumour suppressors and are frequently downregulated in many types of malignancies, including PC. As the family name indicates, ING proteins are able to inhibit cell growth and tumour development via regulation of cell cycle and cancer-relevant pathways such as apoptosis, cellular senescence, DNA repair, cell migration, invasion, and angiogenesis. Many ING splice variants that enhance the diversity of ING activity were discovered. However, it seems that the existence of multiple ING splice variants is underestimated, since alternative splice variants, such as the AR coregulators ING1 and ING3, counteract full-length ING and thus play an opposite functional role. These results open a novel prospective investigation direction in understanding ING factors biology in PC and other malignancies.

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Section: Tumour Suppressive Pathways Of Ing Factorsmentioning

confidence: 99%

Section: Tumour Suppressive Pathways Of Ing Factorsmentioning

confidence: 99%

Section: Ing Factors Regulate Emtmentioning

confidence: 99%

Section: The Role Of Ing Isoforms and Splice Variantsmentioning

confidence: 99%

Section: The Role Of Ing Isoforms and Splice Variantsmentioning

confidence: 99%

See 3 more Smart Citations

ING Tumour Suppressors and ING Splice Variants as Coregulators of the Androgen Receptor Signalling in Prostate Cancer

Melekhova

Baniahmad

2021

Cells

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Molecular mechanisms of inhibitor of growth (ING) family members in health and malignancy

et al. 2022

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ING genes belong to family of tumor suppressor genes with regulatory functions on cell proliferation, apoptosis, and cellular senescence. These include a family of proteins with 5 members (ING1-5), which are downregulated in human malignancies and/or affected by pathogenic mutations. ING proteins are highly evolutionarily conserved proteins containing several domains through which bind to chromatin structures by exerting their effects as readers of histone modification marks, and also binding to proteins like p53 involved in biological processes such as cell cycle regulation. Further, they are known as subunits of histone acetylation as well as deacetylation complexes and so exert their regulatory roles through epigenetic mechanisms. Playing role in restriction of proliferative but also invasive potentials of normal cells, INGs are particularly involved in cancer development and progression. However, additional studies and experimental confirmation are required for these models. This paper highlights the potential impact that INGs may have on the development of human cancer and explores what new information has recently arise on the functions of ING genes.

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Deciphering the dual roles of PHD finger proteins from oncogenic drivers to tumor suppressors

Fan,

Jiang,

Zhou

et al. 2024

Front. Cell Dev. Biol.

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PHD (plant homeodomain) finger proteins emerge as central epigenetic readers and modulators in cancer biology, orchestrating a broad spectrum of cellular processes pivotal to oncogenesis and tumor suppression. This review delineates the dualistic roles of PHD fingers in cancer, highlighting their involvement in chromatin remodeling, gene expression regulation, and interactions with cellular signaling networks. PHD fingers’ ability to interpret specific histone modifications underscores their influence on gene expression patterns, impacting crucial cancer-related processes such as cell proliferation, DNA repair, and apoptosis. The review delves into the oncogenic potential of certain PHD finger proteins, exemplified by PHF1 and PHF8, which promote tumor progression through epigenetic dysregulation and modulation of signaling pathways like Wnt and TGFβ. Conversely, it discusses the tumor-suppressive functions of PHD finger proteins, such as PHF2 and members of the ING family, which uphold genomic stability and inhibit tumor growth through their interactions with chromatin and transcriptional regulators. Additionally, the review explores the therapeutic potential of targeting PHD finger proteins in cancer treatment, considering their pivotal roles in regulating cancer stem cells and influencing the immune response to cancer therapy. Through a comprehensive synthesis of current insights, this review underscores the complex but promising landscape of PHD finger proteins in cancer biology, advocating for further research to unlock novel therapeutic avenues that leverage their unique cellular roles.

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A Novel Splice Variant of the Inhibitor of Growth 3 Lacks the Plant Homeodomain and Regulates Epithelial–Mesenchymal Transition in Prostate Cancer Cells

Cited by 5 publications

References 36 publications

ING Tumour Suppressors and ING Splice Variants as Coregulators of the Androgen Receptor Signalling in Prostate Cancer

ING Tumour Suppressors and ING Splice Variants as Coregulators of the Androgen Receptor Signalling in Prostate Cancer

Molecular mechanisms of inhibitor of growth (ING) family members in health and malignancy

Deciphering the dual roles of PHD finger proteins from oncogenic drivers to tumor suppressors

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