Chromobox homolog 8 (CBX8) Interacts with Y-Box binding protein 1 (YBX1) to promote cellular proliferation in hepatocellular carcinoma cells

Xiao, Lushan; Zhou, Zixiao; Li, Wenwen; Peng, Jie; Sun, Qingcan; Zhu, Hongbo; Song, Yang; Hou, Jilun; Sun, Jiaqian; Cao, Hui-Chuan; Dong, Zhong‐Yi; Wu, De‐Hua; Liu, Li

doi:10.18632/aging.102241

Cited by 19 publications

(15 citation statements)

References 43 publications

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“…Besides, KPNA2 has been found to interact with Chromobox 8 (CBX8) in human lung adenocarcinoma cancer cells [15]. Expression of CBX8, which is a member of the polycomb family of epigenetic transcription factors, correlates with tumorigenesis in HCC and esophageal squamous cell carcinoma [16][17][18]. Additionally, the high expression of CBX8 has been elaborated to foreshadow unsatisfactory overall survival and disease-free survival (DFS) of patients with muscle invasive BCa [19].…”

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confidence: 99%

KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway

Zeng

Luo

et al. 2021

J Transl Med

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Background Bladder cancer (BCa) is a common malignancy characterized by high heterogeneity, yet the current treatment modalities are limited. The aim of the present investigation was to unravel the functional role of Karyopherin alpha 2 (KPNA2), a tumor facilitator identified in multiple malignancies, in the progression of BCa. Methods BCa tissues and adjacent normal tissues were surgically resected and analyzed from patients with BCa to determine the expression profile of KPNA2 and Chromobox 8 (CBX8) by RT-qPCR, Western blot analysis and immunohistochemistry. The relationship among KPNA2, CBX8 and PR domain zinc finger protein 1 (PRDM1) was explored by co-immunoprecipitation and chromatin-immunoprecipitation. The functions of KPNA2, CBX8 and PRDM1 on BCa cell proliferation, migration and invasion were evaluated. Next, a nude mouse model of BCa was established for validating the roles of KPNA2, CBX8 and PRDM1 in vivo. Results KPNA2 and CBX8 were highly expressed in BCa and are in association with dismal oncologic outcomes of patients with BCa. KPNA2 promoted nuclear import of CBX8. CBX8 downregulated PRDM1 by recruiting BCOR in the promoter region of PRDM1. Overexpression of KPNA2 promoted the malignant behaviors of BCa cells, which was counteracted by silencing of CBX8. Overexpressing PRDM1 attenuated the progression of BCa by inhibiting c-FOS expression. The tumor-promoting effects of KPNA2 via the PRDM1/c-FOS pathway were also validated in vivo. Conclusion Collectively, our findings attached great importance to the interplay between KPNA2 and CBX8 in BCa in mediating the development and progression of BCa, thus offering a promising candidate target for better BCa patient management.

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confidence: 99%

KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway

Zeng

Luo

et al. 2021

J Transl Med

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“…3A). CBX8 exerts cancer-promoting effects on a variety of malignant tumors, such as liver, colon and esophageal cancer (20)(21)(22)(23)(24)(25). The WT and MUT 3'-UTR (mutated at positions 617-623) sequences of CBX8 were cloned into the pGL6-miR vector.…”

Section: Resultsmentioning

confidence: 99%

“…It has been reported that, in hepatocellular carcinoma, CBX8 exhibits oncogenic activity through AKT/β-catenin activation (20,21). It has also been demonstrated to interact with Y-Box binding protein 1 (YBX1) to promote the proliferation of liver cancer cells (22). CBX8 promoted tumorigenesis and radiation tolerance of esophageal squamous cell carcinoma cells by targeting APAF1 (23).…”

Section: Discussionmentioning

confidence: 99%

hsa‑miR‑429 targets CBX8 to promote cell apoptosis in diffuse large B‑cell lymphoma

Liang

Liu

et al. 2021

Mol Med Rep

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Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide. Several studies have indicated that Homo sapiens (hsa)-microRNA (miR)-429 exerts a tumor-suppressive effect on a variety of malignant tumors. To the best of our knowledge, the molecular function and mechanism of action of hsa-miR-429 in DLBCL have not been evaluated to date. The present study demonstrated that the expression of hsa-miR-429 in DLBCL cells was significantly reduced. hsa-miR-429 inhibited the proliferation of the DLBCL cell lines, SUDHL-4 and DB, and promoted apoptosis. A dual luciferase reporter assay was used to demonstrate that chromobox 8 (CBX8) was the target gene of hsa-miR-429. Overexpression of CBX8 promoted the proliferation of SUDHL-4 and DB cells and inhibited apoptosis, thereby playing a cancer-promoting role. Transfection of hsa-miR-429 mimic into DB cells overexpressing CBX8 antagonized the effect of CBX8 on the proliferation of DB cells. Moreover, the apoptotic rate was increased in DB cells overexpressing CBX8 and transfected with hsa-miR-429 mimic, while the proportion of cells in the G 2 /M phase was significantly reduced. These results demonstrated the antagonistic effect of hsa-miR-429 on the oncogenic function of CBX8. Therefore, in DLBCL, the tumor suppressor effect of hsa-miR-429 may be achieved by targeted downregulation of CBX8, suggesting that hsa-miR-429 may be used as a diagnostic marker and a potential nucleic acid drug for DLBCL. CBX8 may also represent an effective therapeutic target for DLBCL.

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“…Further research indicates that these functions of CBX8 are mainly exerted by H3K27me3's control of the transcriptional expression of bone morphogenetic protein 4 (BMP4) and regulation of Smads and mitogen-activated protein kinase (MAPK) signaling pathways. It has also been shown that CBX8 exhibits oncogenic activity by activating the Akt/β-catenin signaling pathway in HCC (9,61,62).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the prognosis for chromobox family in gastric cancer

Kang

Zhu

et al. 2020

J Gastrointest Oncol

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Background: Chromobox (CBX) family proteins are a class of transcriptional repressors involved in epigenetic regulation and developmental processes of various tumors, including gastric cancer. However, the function and prognosis of different CBXs in gastric cancer remain unknown. Methods: This study addresses this issue by synthesizing several mainstream databases (Oncomine, GEPIA2, cBioportal, and Kaplan-Meier plotter, among others) that currently contain many tumor samples and provide very reliable analysis results, investigating the role of CBXs in the prognosis of gastric cancer. Results: The mRNA of CBX1/2/3/4/5/8 was highly expressed in gastric cancer, the mRNA of CBX7 was lowly expressed in gastric cancer, and the mRNA expression of CBX6 was not significantly different in CRC. Besides, high and low CBXs mRNA expression correlated with cancer stage, node metastasis status, H. pylori infection status, and tumor grade in CRC patients. We found that high mRNA expression of CBX4/5/6/7/8 was significantly associated with worse overall survival (OS), progression-free survival (FP), and post-progression survival (PPS) in a large number of CRC patients. High mRNA expression of CBX3 was significantly associated with better OS and FP. We also found that none of the eight CBXs family genes had a mutation rate of less than 5% in gastric cancer, and the highest mutation rate was in CBX3 (14%). Conclusions: These results suggest that CBX3/4/5/6/7/8 could be a prognostic biomarker in gastric cancer patients.

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Chromobox homolog 8 (CBX8) Interacts with Y-Box binding protein 1 (YBX1) to promote cellular proliferation in hepatocellular carcinoma cells

Cited by 19 publications

References 43 publications

KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway

KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway

hsa‑miR‑429 targets CBX8 to promote cell apoptosis in diffuse large B‑cell lymphoma

Comprehensive analysis of the prognosis for chromobox family in gastric cancer

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