TRIM22 inhibits osteosarcoma progression through destabilizing NRF2 and thus activation of ROS/AMPK/mTOR/autophagy signaling

Liu, Wei; Zhao, Yuechao; Wang, Guangfu; Feng, Shuang; Ge, Xuhui; Wu, Ye; Wang, Zhuanghui; Zhu, Yufeng; Cai, Wei; Bai, Jianling; Zhou, Xuhui

doi:10.1016/j.redox.2022.102344

Cited by 93 publications

(44 citation statements)

References 53 publications

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“…Further correlation analysis found BNIP3 to have a significantly positive correlation with MYC, NELL1, SAR1A, PLOD2, and other genes proven to promote osteosarcoma metastasis [ 18 , 19 , 20 , 21 ]. However, a significantly negative correlation was found between TNFAIP8L1, TRIM22, and other genes proven to inhibit osteosarcoma metastasis [ 22 , 23 ]. In addition, pan-cancer analysis revealed that BNIP3 was also differentially expressed in different tumor tissues compared to that in normal tissues, including LAML, COAD, and KIRC, which was consistent with previous studies [ 24 , 25 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

Huang

Sun

Liu

et al. 2023

Cancers

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Background: The defense response is a type of self-protective response of the body that protects it from damage by pathogenic factors. Although these reactions make important contributions to the occurrence and development of tumors, the role they play in osteosarcoma (OS), particularly in the immune microenvironment, remains unpredictable. Methods: This study included the clinical information and transcriptomic data of 84 osteosarcoma samples and the microarray data of 12 mesenchymal stem cell samples and 84 osteosarcoma samples. We obtained 129 differentially expressed genes related to the defense response (DRGs) by taking the intersection of differentially expressed genes with genes involved in the defense response pathway, and prognostic genes were screened using univariate Cox regression. Least absolute shrinkage and selection operator (LASSO) penalized Cox regression and multivariate Cox regression were then used to establish a DRG prognostic signature (DGPS) via the stepwise method. DGPS performance was examined using independent prognostic analysis, survival curves, and receiver operating characteristic (ROC) curves. In addition, the molecular and immune mechanisms of adverse prognosis in high-risk populations identified by DGPS were elucidated. The results were well verified by experiments. Result: BNIP3, PTGIS, and ZYX were identified as the most important DRGs for OS progression (hazard ratios of 2.044, 1.485, and 0.189, respectively). DGPS demonstrated outstanding performance in the prediction of OS prognosis (area under the curve (AUC) values of 0.842 and 0.787 in the training and test sets, respectively, adj-p < 0.05 in the survival curve). DGPS also performed better than a recent clinical prognostic approach with an AUC value of only 0.674 [metastasis], which was certified in the subsequent experimental results. These three genes regulate several key biological processes, including immune receptor activity and T cell activation, and they also reduce the infiltration of some immune cells, such as B cells, CD8+ T cells, and macrophages. Encouragingly, we found that DGPS was associated with sensitivity to chemotherapeutic drugs including JNK Inhibitor VIII, TGX221, MP470, and SB52334. Finally, we verified the effect of BNIP3 on apoptosis, proliferation, and migration of osteosarcoma cells through experiments. Conclusions: This study elucidated the role and mechanism of BNIP3, PTGIS, and ZYX in OS progression and was well verified by the experimental results, enabling reliable prognostic means and treatment strategies to be proposed for OS patients.

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Section: Discussionmentioning

confidence: 99%

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

Huang

Sun

Liu

et al. 2023

Cancers

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“…In osteosarcoma, TRIM22 can interact with Nrf2 and accelerate its degradation by inducing ubiquitination dependent on its E3 ligase activity, thus activating downstream AMPK/mTOR signaling, and affecting Nrf2-mediated ROS imbalance. Moreover, TRIM22 was found to inhibit the Warburg effect in osteosarcoma cells [ 101 ]. In another study, TRIM15 was identified to promote NSCLC progression via Nrf2 stability mediated by promoting Keap1 (Kelch-like ECH associated protein 1) ubiquitination and degradation [ 94 ].…”

Section: The Trim Family and Cancer Pathologymentioning

confidence: 99%

“…TRIM28 also regulates the degradation of AMPK [ 257 ]. TRIM22 inhibites osteosarcoma progression by promoting proteasomal degradation of NRF2 independent of KEAP1, thereby activating AMPK/mTOR/autophagy signaling that led to autophagic osteosarcoma cell death [ 101 ]. In colorectal cancer, TRIM24 directly interactes with the YAP promoter at the 983 to 734 site and activated YAP transcription, ultimately enhancing the proliferation of cells [ 258 ].…”

Section: The Trim Family and Cancer Pathologymentioning

confidence: 99%

TRIM family contribute to tumorigenesis, cancer development, and drug resistance

et al. 2022

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The tripartite-motif (TRIM) family represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases. TRIM family is involved in a variety of cellular signaling transductions and biological processes. TRIM family also contributes to cancer initiation, progress, and therapy resistance, exhibiting oncogenic and tumor-suppressive functions in different human cancer types. Moreover, TRIM family members have great potential to serve as biomarkers for cancer diagnosis and prognosis. In this review, we focus on the specific mechanisms of the participation of TRIM family members in tumorigenesis, and cancer development including interacting with dysregulated signaling pathways such as JAK/STAT, PI3K/AKT, TGF-β, NF-κB, Wnt/β-catenin, and p53 hub. In addition, many studies have demonstrated that the TRIM family are related to tumor resistance; modulate the epithelial–mesenchymal transition (EMT) process, and guarantee the acquisition of cancer stem cells (CSCs) phenotype. In the end, we havediscussed the potential of TRIM family members for cancer therapeutic targets.

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“…Osteosarcoma ranks first among malignant bone-related cancers in adolescents and has a complex heterogeneity and an abnormally produced immature osteoid matrix. [1][2][3] Currently, the standard treatments for osteosarcoma are neoadjuvant chemotherapy (presurgery), surgical resection, and adjuvant chemotherapy (postsurgery). 4,5 Despite the efforts of researchers, there has been no significant improvement in the 5-year survival rate of osteosarcoma patients over the past few decades, suggesting that existing therapeutic strategies are insufficient.…”

Section: Introductionmentioning

confidence: 99%

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Tian

Cao

et al. 2023

Bone Res

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Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding the efforts of researchers, its five-year survival rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis. Therefore, managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease. Additionally, given the advances in nanomedicine, there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics. Here, we review the classification, characteristics, and functions of the key components of the immune microenvironment in osteosarcoma. This review also emphasizes the application, progress, and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment. Furthermore, we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

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TRIM22 inhibits osteosarcoma progression through destabilizing NRF2 and thus activation of ROS/AMPK/mTOR/autophagy signaling

Cited by 93 publications

References 53 publications

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

TRIM family contribute to tumorigenesis, cancer development, and drug resistance

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

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