Overexpression of PRDM5 promotes acute myeloid leukemia cell proliferation and migration by activating the JNK pathway

Zhou, Pan; Chen, Xing; Li, Mengke; Sun, Xiaolu; Tan, Jiaqi; Wang, Xiaomin; Chu, Yajing; Zhang, Yicheng; Cheng, Tao; Zhou, Jianfeng; Wang, Gaoxiang; Yuan, Weiping

doi:10.1002/cam4.2261

Cited by 5 publications

(4 citation statements)

References 35 publications

(79 reference statements)

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“…PRDM5 gene mutation or dysregulation is related to the pathogenesis of brittle cornea syndrome 7,8 . The prompt effect of PRDM5 on the progression of acute myeloid leukaemia and murine melanoma has been demonstrated by some researchers 9,10 . On the contrary, the establishment of PRDM5 as a tumour suppressor has also been reported in some literatures.…”

Section: Introductionmentioning

confidence: 99%

PRDM5 suppresses oesophageal squamous carcinoma cells and modulates 14–3‐3zeta/Akt signalling pathway

Zhang

Liu²,

Sheng

et al. 2021

Clin Exp Pharma Physio

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Dysregulation of PR (PRDI‐BF1 and RIZ) domain protein 5 (PRDM5) expression has been shown to be associated with the progression of many malignancies. Nevertheless, the role and underlying mechanism of PRDM5 in oesophageal squamous cell carcinoma (ESCC) remain elusive. qRT‐PCR was performed to analyze PRDM5 mRNA expression, and western blot was used to determine protein expression of PRDM5, MMP‐2, MMP‐9, 14–3‐3zeta, pan‐Akt and phosphorylated Akt expression. CCK‐8 staining was employed to evaluate cell proliferation, while wound scratch assay and Transwell assay were carried out to detect cell migration. A tumour xenograft model of ESCC was also established to validate the effect of PRDM5. PRDM5 expression was downregulated in ESCC tissues and positively correlated with the overall survival of ESCC patients. Silencing PRDM5 expression promoted cell proliferation in ESCC cells, while overexpressing PRDM5 inhibited cell proliferation. Moreover, the migratory abilities of ESCC cells were promoted by PRDM5 knockdown but were attenuated by PRDM5 overexpression. Importantly, 14–3‐3zeta expression, along with the phosphorylation of Akt, was suppressed by PRDM5 in ESCC cells. In the established tumour xenograft model, PRDM5 regulated ESCC tumour growth as well as the expression of 14–3‐3zeta and phosphorylation of Akt protein. In conclusion, PRDM5 suppresses ESCC cell proliferation and migration and negatively regulates 14–3‐3zeta/Akt signalling pathway in vitro and in vivo.

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Section: Introductionmentioning

confidence: 99%

PRDM5 suppresses oesophageal squamous carcinoma cells and modulates 14–3‐3zeta/Akt signalling pathway

Zhang

Liu²,

Sheng

et al. 2021

Clin Exp Pharma Physio

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“…JNK pathway was implicated in the antineoplastic effects of CPPTL against acute myeloid leukaemia [21]. Activation of JNK promoted the suppressive effect of haem oxygenase-1 on acute myeloid leukaemia cell apoptosis [22], and silence of PR/SET domain 5 suppressed activation of JNK to inhibit the acute myeloid leukaemia cell proliferation [23]. Our results showed that protein expression of JNK phosphorylation was decreased by over-expression of OSR1 in acute myeloid leukaemia cells, while increased by the silence of OSR1.…”

Section: Discussionmentioning

confidence: 55%

OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling

Zong

Sun

2021

Autoimmunity

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Odd-skipped related transcription factor 1 (OSR1) is implicated in various pathophysiologic processes, such as embryonic heart and urogenital formation, and functions as a tumour suppressor in diverse tumours. Regardless, the regulatory role and mechanism of OSR1 in acute myeloid leukaemia are scarce. Firstly, the CD34-positive blasts or the normal blasts were isolated from the plasma samples of acute myeloid leukaemia patients or healthy donors, respectively. Expression of OSR1 analysis by western blot and qRT-PCR showed that OSR1 was reduced in CD34-positive blasts and acute myeloid leukaemia cell lines. Secondly, acute myeloid leukaemia cell lines were transfected with pcDNA vector or shRNA for the over-expression or silence of OSR1, respectively. Functional assays demonstrated that ectopic expression of OSR1 decreased cell viability and repressed the proliferation of acute myeloid leukaemia cells, while promoted the cell apoptosis. Silence of OSR1 contributed to the proliferation of acute myeloid leukaemia cells and suppressed the cell apoptosis. Thirdly, over-expression of OSR1 decreased protein expression of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and JNK phosphorylation in the acute myeloid leukaemia cells. Ectopic expression of LGR5 attenuated OSR1 over-expression-induced decrease of LGR5 and JNK phosphorylation. Lastly, ectopic expression of LGR5 attenuated OSR1 over-expression-induced decrease of cell viability and proliferation in acute myeloid leukaemia cells. In conclusion, OSR1 functioned as a tumour suppressor in acute myeloid leukaemia cells by inhibiting LGR5-mediated activation of JNK signalling.

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“…However, there are exceptions. In melanoma and acute myelogenous leukemia, PRDM5 is overexpressed in tumor cells and is believed to promote tumor progression through activation of the JNK pathway [25,26]. This opposite regulatory function may be due to its special role in transcriptional regulation.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of promoter methylation gene PRDM5 contributes to the development of tumor proliferation and predicts poor prognosis in gastric cancer

et al. 2021

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Background: Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Previous studies have shown that PRDM5 is methylated and silenced in GC. However, the role of PRDM5 in GC progression has not been explored. Methods: The expression and epigenetic alterations of PRDM5 in GC were analyzed in public datasets. The mRNA and protein expression of PRDM5 in fresh tissues were detected by semi-quantitative PCR and Western blot. And expression of PRDM5 in gastric paracarcinoma and carcinoma tissues from 162 patients was detected by immunohistochemistry (IHC) and assessed the association with different clinicopathological features. The prognostic value of PRDM5 in GC patients was evaluated using Kaplan-Meier plotter. We also studied promoter region methylation of PRDM5 in GC by methylation-specific PCR (MSP). The effects of PRDM5 on cell proliferation and migration were conducted by functional experiments in vitro. Results: The expression of PRDM5 was downregulated in GC, and that was associated with poor survival and tumor progression. And PRDM5 expression was found to be an independent prognostic factor for GC. We also found that the methylation of PRDM5 promoter was closely related to the histopathological types and the progression of tumors through the public relations database. In vitro, ectopical expression of PRDM5 inhibited the growth of tumor cells, while knockdown of PRDM5 increased the proliferation and migration of tumor cells. Conclusion:These results suggest that PRDM5 may be a novel TSG methylated in GC that plays important roles in GC development. And we found PRDM5 as a potential survival biomarker for GC, especially in well differentiated GC. PRDM5 expression was significantly correlated with tumor stage and histological type.

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Overexpression of PRDM5 promotes acute myeloid leukemia cell proliferation and migration by activating the JNK pathway

Cited by 5 publications

References 35 publications

PRDM5 suppresses oesophageal squamous carcinoma cells and modulates 14–3‐3zeta/Akt signalling pathway

PRDM5 suppresses oesophageal squamous carcinoma cells and modulates 14–3‐3zeta/Akt signalling pathway

OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling

Downregulation of promoter methylation gene PRDM5 contributes to the development of tumor proliferation and predicts poor prognosis in gastric cancer

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