The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

Zacharopoulou, Nefeli; Tsapara, Anna; Kallergi, Galatea; Schmid, Evi; Alkahtani, Saad; Alarifi, Saud; Tsichlis, Philip N.; Kampranis, Sotirios C.; Stournaras, Christos

doi:10.1159/000489917

Cited by 19 publications

(30 citation statements)

References 33 publications

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“…Evident from Fan et al corroborated that KDM2B accelerated cell proliferation in triple‐negative breast cancer cells via repression of p15 INK4B , p16 INK4A , and p57 KIP2 transcription (Zheng et al, ). Otherwise, KDM2B was also proven to mediate epithelial‐mesenchymal transition process and small GTPases in colon cancer cells (Zacharopoulou, Tsapara, Kallergi, Schmid, Alkahtani, et al, ). In the actual research, we attempted to uncover whether KDM2B acetylation triggered by CBP could affect the carcinogenesis of colon cancer.…”

Section: Discussionmentioning

confidence: 99%

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Retracted: CBP‐triggered KDM2B acetylation accelerates the carcinogenesis of colon cancer

Zhao

2019

Journal Cellular Physiology

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Lysine (K)-specific demethylase 2B (KDM2B) has been testified to be an oncogene in diverse cancers, which joins in mediating the carcinogenesis of cancers. Nonetheless, the function of KDM2B in colon cancer remains unexplored. The study attempted to disclose the influences of KDM2B acetylation in the progression of colon cancer.SW48 and SUN-C1 cells were transfected with Flag-KDM2B and administrated by trichostatin A and nicotinamide for 24 hr. Immunoprecipitation with a Flag antibody followed by western blot with acetyl-lysine-specific antibody was executed to detect KDM2B acetylation. The correlation between CREB binding protein (CBP) and KDM2B was then investigated. The K-R and K-Q mutants were constructed and the impacts of KDM2B on demethylation of nucleosomal substrates, p21, and puma transcription and the carcinogenesis of colon cancer were probed. CBP immediately evoked KDM2B acetylation at lysine residue 765 in colon cancer cells. Acetylation of KDM2B obviously destroyed the relevance with nucleosomes, demethylation of nucleosomal substrates, and repressed p21 and puma transcription. More important, KDM2B acetylation restrained SUN-C1 cells proliferation and colony formation, meanwhile, hindered cell migration and invasion. Beyond that, the tumor formation was repressed by KDM2B acetylation. The observations testified that CBP-triggered KDM2B acetylation accelerated the carcinogenesis of colon cancer. K E Y W O R D S acetylation, colon cancer, CREB binding protein, lysine (K)-specific demethylase 2B

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Section: Discussionmentioning

confidence: 99%

“…Otherwise, KDM2B was also proven to mediate epithelial-mesenchymal transition process and small GTPases in colon cancer cells (Zacharopoulou, Tsapara, Kallergi, Schmid, Alkahtani, et al, 2018). In the actual research, we attempted to uncover whether KDM2B acetylation triggered by CBP could affect the carcinogenesis of colon…”

Section: Discussionmentioning

confidence: 99%

Retracted: CBP‐triggered KDM2B acetylation accelerates the carcinogenesis of colon cancer

Zhao

2019

Journal Cellular Physiology

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“…KDM2B functions as an oncogene in several types of tumors. Following the original discovery of its oncogenic potential in Moloney murine leukemia virus (MoMuLV)-induced rodent T cell lymphomas, where it was found to be activated by provirus integration Tzatsos et al, 2009), it has been shown to function as an oncogene in human lymphoid (Andricovich et al, 2016) and myeloid malignancies (van den Boom et al, 2016) as well as in bladder cancer (Kottakis et al, 2011) (McNiel andTsichlis, 2017) and pancreatic cancer (Tzatsos et al, 2013), basal-like breast cancer (Kottakis et al, 2014), gliomas (Wang et al, 2018) and prostate cancer (Zacharopoulou et al, 2018). The oncogenic potential of KDM2B is mediated by multiple mechanisms.…”

Section: Introductionmentioning

confidence: 99%

The inhibition of KDM2B promotes the differentiation of basal-like breast cancer cells via the posttranslational destabilization of SLUG

Fraile

Chavdoula

Laliotis

et al. 2020

Preprint

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KDM2B is a JmjC domain H3K36me2/H3K36me1 demethylase, which immortalizes cells in culture and contributes to the biology of both embryonic and adult stem and progenitor cells. It also functions as an oncogene that contributes to the self-renewal of breast cancer stem cells by regulating polycomb complexes. Here we show that the silencing of KDM2B results in the downregulation of SNAI2 (SLUG), SNAI1 (SNAIL) and SOX9, which also contribute to the biology of mammary stem and progenitor cells. The downregulation of these molecules is posttranscriptional and in the case of the SNAI2-encoded SLUG, it is due to calpain-dependent proteolytic degradation. Mechanistically, the latter depends on the activation of calpastatin-sensitive classical calpain(s) and on the phosphorylation-dependent inhibition of GSK3 via paracrine mechanisms. GSK3 inhibition sensitizes its target SLUG to classical calpains, which are activated by Ca2+ influx and calpastatin downregulation. The degradation of SLUG, induced by the KDM2B knockdown, promotes the differentiation of breast cancer stem cells in culture and reveals an unexpected mechanism of stem cell regulation by a histone demethylase.

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“…35,36 Induction of the EMT promotes cell invasion, migration, and metastasis, which confers stem-celllike characteristics on cancer cells, and induces therapeutic resistance. 37,38 Cellular signaling responses to hypoxia and inflammation involve crosstalk through upregulation of HIF-1α and associated tumorigenic activities, which are mediated by the inflammatory cytokine interferon-α. In addition, expression of HIF-1α is related to EMT.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circPIP5K1A promotes non‐small cell lung cancer proliferation and metastasis through miR‐600/HIF‐1α regulation

Chi

Luo

Song

et al. 2019

J of Cellular Biochemistry

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Circular RNAs (circRNAs) have an important function in human diseases, especially in cancer. circRNA hsa_circ_0014130 (circPIP5K1A), a particularly abundant circRNA, participates in the tumorigenesis of non‐small cell lung cancer (NSCLC), although the underlying regulatory mechanism remains unclear. Here, we investigated the circPIP5K1A role in NSCLC. Expression of circPIP5K1A in NSCLC cell lines was explored with quantitative real‐time PCR. The effect of circPIP5K1A on NSCLC was evaluated with circPIP5K1A silencing, miR‐600 mimic transfection, and hypoxia‐inducible factor (HIF)‐1α overexpression, followed by assessment of cell proliferation, metastasis, and tumorigenesis in nude mice. The subcellular localization of circPIP5K1A was evaluated via fluorescence in situ hybridization (FISH), and correlation between circPIP5K1A, miR‐600, and HIF‐1α was assessed by luciferase assay. The data demonstrated that circPIP5K1A expression was increased in NSCLC cells. FISH showed that circPIP5K1A localized to the cytoplasm. The circPIP5K1A knockdown suppressed NSCLC cell metastasis and proliferation by promoting expression of miR‐600. Overexpression of miR‐600 inhibited HIF‐1α‐mediated metastasis and proliferation of NSCLC cell by downregulating the endothelial mesenchymal transition‐related proteins, Snail and vimentin, and upregulating E‐cadherin. In vivo experiments illustrated that circPIP5K1A silence suppressed tumor growth and pulmonary metastasis. The circPIP5K1A may function as an miR‐600 sponge to facilitate NSCLC proliferation and metastasis by promoting HIF‐1α. A bifluorescein reporter experiment confirmed that miR‐600 was the circPIP5K1A target, and miR‐600 interacted with the 3′ untranslated region of HIF‐1α. These results show that circPIP5K1A acted as a tumor promoter through a novel circPIP5K1A/miR‐600/HIF‐1α axis, which provides candidate markers and therapeutic targets for NSCLC.

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The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

Cited by 19 publications

References 33 publications

Retracted: CBP‐triggered KDM2B acetylation accelerates the carcinogenesis of colon cancer

Retracted: CBP‐triggered KDM2B acetylation accelerates the carcinogenesis of colon cancer

The inhibition of KDM2B promotes the differentiation of basal-like breast cancer cells via the posttranslational destabilization of SLUG

Circular RNA circPIP5K1A promotes non‐small cell lung cancer proliferation and metastasis through miR‐600/HIF‐1α regulation

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