CBX3 accelerates the malignant progression of glioblastoma multiforme by stabilizing EGFR expression

Peng, Wen; Shi, Shuang; Zhong, Jiacheng; Liang, Hui; Hou, Jianbin; Hu, Xiaosong; Wang, Feng; Zhang, Jiayi; Geng, Shengjun; Sun, Xiaochuan; Zhong, Dong; Cui, Hongjuan

doi:10.1038/s41388-022-02296-9

Cited by 19 publications

(15 citation statements)

References 58 publications

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“…And CBX3 expression was regulated by PSMC4. Previous study showed that CBX3 could regulate EGFR expression, which could promote PI3K/AKT/mTOR pathway 15–17 . In this study, our results indicated that CBX3 promoted EGFR expression, and PSMC4 knockdown inhibited EGFR‐PI3K‐AKT‐mTOR signalling by medicating CBX3, whereas PSMC4 promoted EGFR‐PI3K‐AKT‐mTOR signalling.…”

Section: Discussionsupporting

confidence: 57%

“…To further verify the relationship of PSMC4 and CBX3, co‐IP assay was performed, and result showed that PSMC4 directly bond to CBX3, and regulated CBX3 protein expression (Figure 4H). Previous studies showed that CBX3 could regulate EGFR expression, which could promote PI3K/AKT/mTOR pathway 15–17 . To explore how does CBX3 regulate PI3K/AKT/mTOR, co‐IP assay was performed.…”

Section: Resultsmentioning

confidence: 99%

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PSMC4 promotes prostate carcinoma progression by regulating the CBX3–EGFR‐PI3K‐AKT‐mTOR pathway

Liu

Zhang

Gong

et al. 2023

J Cellular Molecular Medi

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Proteasome 26S subunit ATPase 4 (PSMC4) could regulate cancer progression. However, the function of PSMC4 in prostate carcinoma (PCa) progression requires further clarification. In the study, PSMC4 and chromobox 3 (CBX3) levels were verified by TCGA data and tissue microarrays. Cell counting kit‐8, cell apoptosis, cell cycle, wound healing, transwell and xenograft tumour model assays were performed to verify biological functions of PSMC4 in PCa. RNA‐seq, PCR, western blotting and co‐IP assays were performed to verify the mechanism of PSMC4. Results showed that PSMC4 level was significantly increased in PCa tissues, and patients with PCa with a high PSMC4 level exhibited shorter overall survival. PSMC4 knockdown markedly inhibited cell proliferation, cell cycle and migration in vitro and in vivo, and significantly promoted cell apoptosis. Then further study revealed that CBX3 was a downstream target of PSMC4. PSMC4 knockdown markedly reduced CBX3 level, and inhibited PI3K‐AKT‐mTOR signalling. CBX3 overexpression markedly promoted epidermal growth factor receptor (EGFR) level. Finally, PSMC4 overexpression showed reverse effect in DU145 cells, and the effects of PSMC4 overexpression on cell proliferation, migration and clonal formation were rescued by the CBX3 knockdown, and regulated EGFR‐PI3K‐AKT‐mTOR signalling. In conclusion, PSMC4 could regulate the PCa progression by mediating the CBX3‐EGFR‐PI3K‐AKT‐mTOR pathway. These findings provided a new target for PCa treatment.

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Section: Discussionsupporting

confidence: 57%

Section: Resultsmentioning

confidence: 99%

PSMC4 promotes prostate carcinoma progression by regulating the CBX3–EGFR‐PI3K‐AKT‐mTOR pathway

Liu

Zhang

Gong

et al. 2023

J Cellular Molecular Medi

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“…The EGFR-specific E3 ligase is parkin. Parkin increases EGFR ubiquitination and inhibits GBM [ 39 ]. Moreover, parkin ubiquitinates pyruvate kinase M2 (PKM2).…”

Section: Discussionmentioning

confidence: 99%

Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction

Hong

Tsai

et al. 2023

Cells

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Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we cloned and sequenced a splice variant of the hydroxysteroid-like 11-β dehydrogenase 1 gene (HSD11B1L) and named it HSD11B1L-181. HSD11 B1L-181 was specifically expressed only in GBM cells. Overexpression of this variant can significantly promote the proliferation, migration and invasion of GBM cells. Knockdown of HSD11B1L-181 expression inhibited the oncogenic potential of GBM cells. Furthermore, we identified the direct interaction of parkin with HSD11B1L-181 by screening the GBM cDNA expression library via yeast two-hybrid. Parkin is an RBR E3 ubiquitin ligase whose mutations are associated with tumorigenesis. Small interfering RNA treatment of parkin enhanced the proliferative, migratory and invasive abilities of GBM. Finally, we found that the alkaloid peiminine from the bulbs of Fritillaria thunbergii Miq blocks the interaction between HSD11B1L-181 and parkin, thereby lessening carcinogenesis of GBM. We further confirmed the potential of peiminine to prevent GBM in cellular, ectopic and orthotopic xenograft mouse models. Taken together, these findings not only provide insight into GBM, but also present an opportunity for future GBM treatment.

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“…Small-hairpin shRNAs for ARIH2 and p21 and a negative control shRNA (shGFP) were obtained from Gene Pharma Co. Ltd. (Shanghai, China) and were inserted into the pLKO.1 vector [ 21 ]. The ubiquitination plasmid that contained an HA tag was purchased from Addgene (Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

ARIH2 regulates the proliferation, DNA damage and chemosensitivity of gastric cancer cells by reducing the stability of p21 via ubiquitination

et al. 2022

Self Cite

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Ariadne homolog 2 (ARIH2) is a key member of the RING-between-RING (RBR) E3 ligase family, which is characterized by an RBR domain involved in the polyubiquitination process. However, the molecular mechanism and biological function of ARIH2 in the pathogenesis of gastric cancer remain unclear. In this paper, we found that high ARIH2 expression is correlated with poor prognosis in gastric cancer patients and that ARIH2 can significantly promote the proliferation of gastric cancer cells. The effect of ARIH2 knockdown on colony formation and tumorigenesis of gastric cancer cells was also shown both in vivo and in vitro. Further mechanistic investigations revealed that ARIH2 interacts with p21 and induces p21 ubiquitination, and that the K48 residue of ubiquitin and the K161 residue of p21 play key roles in ARIH2-mediated p21 ubiquitination. We identified ARIH2 as an E3 ligase of p21 by an in vitro ubiquitination assay. In addition, ARIH2 knockdown induced DNA damage, and then induced cell apoptosis and regulated the chemosensitivity of gastric cancer cells after combined treatment with 5-fluorouracil. Generally, our results indicated that ARIH2 promotes the proliferation of gastric cancer cells and regulates p21 expression. These data demonstrate the need to further evaluate the potential therapeutic implications of ARIH2 in gastric cancer.

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CBX3 accelerates the malignant progression of glioblastoma multiforme by stabilizing EGFR expression

Cited by 19 publications

References 58 publications

PSMC4 promotes prostate carcinoma progression by regulating the CBX3–EGFR‐PI3K‐AKT‐mTOR pathway

PSMC4 promotes prostate carcinoma progression by regulating the CBX3–EGFR‐PI3K‐AKT‐mTOR pathway

Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction

ARIH2 regulates the proliferation, DNA damage and chemosensitivity of gastric cancer cells by reducing the stability of p21 via ubiquitination

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