CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression

Zhang, Huan; Yu, Haixin; Ren, Dianyuan; Sun, Yan; Guo, Feng; Cai, Hongkun; Zhou, Chen; Zhou, Yingke; Jin, Xin; Wu, Heshui

doi:10.7150/ijbs.68995

Cited by 16 publications

(6 citation statements)

References 41 publications

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“…The data revealed that 29 genes were dysregulated after CDK4/6 inhibitor or BET inhibitors treatment and were associated with PC sensitivity to CDK4/6 inhibitors (Figure 1A). Interestingly, we found that CBX3, which we had previously studied, [24] was one of the 29 genes (Figure 1A; Figure S1A,B, Supporting Information). It has been reported that CBX3 is involved in regulating the cell cycle of cancer cells.…”

Section: The Cell Cycle-associated Gene Cbx3 Is Directly Regulated By...mentioning

confidence: 78%

“…This finding suggests that CBX3 play a significant role in promoting the development of cancer cells. [ 20 , 24 , 36 ] Aberrant CBX3 expression contributes to the progression of various cancer types through the epigenetic regulation of cancer development and growth‐related genes. [ 27 , 37 ] In PC, CBX3 regulates AR signal transduction activity and promotes c‐MYC expression, thereby contributing to the progression of tumor growth.…”

Section: Discussionmentioning

confidence: 99%

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Targeting CBX3 with a Dual BET/PLK1 Inhibitor Enhances the Antitumor Efficacy of CDK4/6 Inhibitors in Prostate Cancer

Liang,

Yang,

Zeng

et al. 2023

Advanced Science

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The development of castration‐resistant prostate cancer (CRPC) is a significant factor that reduces life expectancy among patients with prostate cancer. Previously, it is reported that CDK4/6 inhibitors can overcome the resistance of CRPC to BET inhibitors by destabilizing BRD4, suggesting that the combination of CDK4/6 inhibitors and BET inhibitors is a promising approach for treating CRPC. In this study, candidates that affect the combined antitumor effect of CDK4/6 inhibitors and BET inhibitors on CRPC is aimed to examine. The data demonstrates that CBX3 is abnormally upregulated in CDK4/6 inhibitors‐resistant cells. CBX3 is almost positively correlated with the cell cycle in multiple malignancies and is downregulated by BET inhibitors. Mechanistically, it is showed that CBX3 is transcriptionally upregulated by BRD4 in CRPC cells. Moreover, it is demonstrated that CBX3 modulated the sensitivity of CRPC to CDK4/6 inhibitors by binding with RB1 to release E2F1. Furthermore, it is revealed that PLK1 phosphorylated CBX3 to enhance the interaction between RB1 and CBX3, and desensitize CRPC cells to CDK4/6 inhibitors. Given that BRD4 regulates CBX3 expression and PLK1 affects the binding between RB1 and CBX3, it is proposed that a dual BRD4/PLK1 inhibitor can increase the sensitivity of CRPC cells to CDK4/6 inhibitors partially through CBX3.

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Section: The Cell Cycle-associated Gene Cbx3 Is Directly Regulated By...mentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Targeting CBX3 with a Dual BET/PLK1 Inhibitor Enhances the Antitumor Efficacy of CDK4/6 Inhibitors in Prostate Cancer

Liang,

Yang,

Zeng

et al. 2023

Advanced Science

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“…Briefly, a luciferase reporter was built by utilizing complementary oligonucleotides that encompassed potential NBR1 binding locations (both types; wild (wt) and mutant (mut) and introducing them into pGL3-control luciferase reporter vectors. The protocol is detailed in our previous articles [ 16 , 26 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

Tumor-associated macrophage-derived exosomes LINC01592 induce the immune escape of esophageal cancer by decreasing MHC-I surface expression

Qiao,

Cheng,

Xue

et al. 2023

J Exp Clin Cancer Res

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Background TAMs (tumor-associated macrophages) infiltration promotes the progression of esophageal cancer (EC). However, the underlying mechanisms remain unclear. Methods Abnormal expression of LINC01592 from EC microarrays of the TCGA database was analyzed. LINC01592 expression level was validated in both EC cell lines and tissues. Stable LINC01592 knockdown and overexpression of EC cell lines were established. In vitro and in vivo trials were conducted to test the impact of LINC01592 knockdown and overexpression on EC cells. RNA binding protein immunoprecipitation (RIP), RNA pulldown assays, and Immunofluorescence (IF) were used to verify the combination of E2F6 and LINC01592. The combination of E2F6 and NBR1 was verified through the utilization of ChIP and dual luciferase reporter assays. Results LINC01592 is carried and transferred by exosomes secreted by M2-TAMs to tumor cells. The molecular mechanism underlying the promotion of NBR1 transcription involves the direct binding of LINC01592 to E2F6, which facilitates the nuclear entry of E2F6. The collaborative action of LINC01592 and E2F6 results in improved NBR1 transcription. The elevation of NBR1 binding to the ubiquitinated protein MHC-I via the ubiquitin domain caused a higher degradation of MHC-I in autophagolysosomes and a reduction in MHC-I expression on the exterior of cancerous cell. Consequently, this caused cancerous cells to escape from CD8+ CTL immune attack. The tumor-promoting impacts of LINC01592, as well as the growth of M2-type macrophage-driven tumors, were significantly suppressed by the interruption of E2F6/NBR1/MHC-I signaling through the effect of siRNA or the corresponding antibody blockade. Significantly, the suppression of LINC01592 resulted in an upregulation of MHC-I expression on the tumor cell membrane, thereby enhancing the efficacy of CD8+ T cell reinfusion therapy. Conclusions The investigation conducted has revealed a significant molecular interaction between TAMs and EC via the LINC01592/E2F6/NBR1/MHC-I axis, which facilitates the progression of malignant tumors. This suggests that a therapeutic intervention targeting this axis may hold promise for the treatment of the disease.

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“…However, to fully activate these T cells, XP-524 must be used in combination with an anti–PD-1 antibody. Additionally, the YBX1/CBX3/SMURF2 signaling axis is a potential target in PC related to smoking, as exposure to cigarette smoke can lead to increased expression of YBX1 and CBX3 220 . The HDAC inhibitor valproic acid has also been shown to enhance the effects of gemcitabine in both in vitro and in vivo PC models, but more clinical trials are needed to determine the safety and efficacy of this combination.…”

Section: Exosomesmentioning

confidence: 99%

The Effect of Intratumor Heterogeneity in Pancreatic Ductal Adenocarcinoma Progression and Treatment

Saleh,

Shihadeh,

Yousef

et al. 2024

Pancreas

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Background and Objectives Pancreatic cancer is one of the most lethal malignancies. Even though many substantial improvements in the survival rates for other major cancer forms were made, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Even more, no standard classification system for pancreatic cancer is based on cellular biomarkers. This review will discuss and provide updates about the role of stem cells in the progression of PC, the genetic changes associated with it, and the promising biomarkers for diagnosis. Materials and Methods The search process used PubMed, Cochrane Library, and Scopus databases to identify the relevant and related articles. Articles had to be published in English to be considered. Results The increasing number of studies in recent years has revealed that the diversity of cancer-associated fibroblasts is far greater than previously acknowledged, which highlights the need for further research to better understand the various cancer-associated fibroblast subpopulations. Despite the huge diversity in pancreatic cancer, some common features can be noted to be shared among patients. Mutations involving CDKN2, P53, and K-RAS can be seen in a big number of patients, for example. Similarly, some patterns of genes and biomarkers expression and the level of their expression can help in predicting cancer behavior such as metastasis and drug resistance. The current trend in cancer research, especially with the advancement in technology, is to sequence everything in hopes of finding disease-related mutations. Conclusion Optimizing pancreatic cancer treatment requires clear classification, understanding CAF roles, and exploring stroma reshaping approaches.

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CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression

Cited by 16 publications

References 41 publications

Targeting CBX3 with a Dual BET/PLK1 Inhibitor Enhances the Antitumor Efficacy of CDK4/6 Inhibitors in Prostate Cancer

Targeting CBX3 with a Dual BET/PLK1 Inhibitor Enhances the Antitumor Efficacy of CDK4/6 Inhibitors in Prostate Cancer

Tumor-associated macrophage-derived exosomes LINC01592 induce the immune escape of esophageal cancer by decreasing MHC-I surface expression

The Effect of Intratumor Heterogeneity in Pancreatic Ductal Adenocarcinoma Progression and Treatment

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