TRIM32 overexpression improves chemoresistance through regulation of mitochondrial function in non-small-cell lung cancers

Du, Yuchen; Zhang, Wei; Du, Binghui; Zang, Sheng; Wang, Xinpeng; Mao, Xin; Hu, Zhansheng

doi:10.2147/ott.s176689

Cited by 16 publications

(12 citation statements)

References 26 publications

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“…TRIM32 exerts a key role in regulating the survival and apoptosis of various cell types. TRIM32 can inhibit the apoptosis of cancer cells and enhances cell survival under exposure to chemotherapeutics [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of TRIM32 Attenuates the Apoptosis, Oxidative Stress and Inflammatory Injury of Podocytes Induced by High Glucose by Affecting the Akt/GSK-3β/Nrf2 Pathway

Chun-hua

Tian

Wang

et al. 2021

Preprint

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Hyperglycemia-induced oxidative stress of podocytes exerts a major role in the pathological process of diabetic nephropathy. Tripartite motif-containing protein 32 (TRIM32) has been reported as a key protein in the modulation of cellular apoptosis and oxidative stress under various pathological processes. However, whether TRIM32 participates in the regulation of high glucose (HG)-induced injury in podocytes has not been investigated. The aims of this work were to assess the possible role of TRIM32 in mediating HG-induced apoptosis, oxidative stress and inflammatory response in podocytes in vitro. Herein, our results showed a marked increase in TRIM32 expression in HG-exposed podocytes. Loss-of-function experiments showed that the knockdown of TRIM32 improved the viability of HG-stimulated podocytes, and suppressed HG-induced apoptosis, oxidative stress and inflammatory response in podocytes. Further investigation revealed that the inhibition of TRIM32 enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with modulation of the Akt/glycogen synthase kinase-3β (GSK-3β) axis in podocytes following HG exposure. However, the suppression of Akt abrogated the TRIM32-knockdown-mediated activation of Nrf2 in HG-exposed podocytes. In addition, the knockdown of Nrf2 markedly abolished the TRIM32-inhibition-induced protective effects in HG-exposed podocytes. In summary, the results of this work show that the inhibition of TRIM32 protects podocytes from HG-induced injury by potentiating Nrf2 signaling via the modulation of Akt/GSK-3β signaling. This study indicates a potential role of TRIM32 in mediating podocyte injury during the progression of diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Inhibition of TRIM32 Attenuates the Apoptosis, Oxidative Stress and Inflammatory Injury of Podocytes Induced by High Glucose by Affecting the Akt/GSK-3β/Nrf2 Pathway

Chun-hua

Tian

Wang

et al. 2021

Preprint

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“…Cell-based assays showed TRIM32 upregulates mitochondrial membrane potential, increases cell proliferation, and reduces cisplatin-induced ROS accumulation. Further, an increase in expression of Bcl2, a known suppressor of mitochondrial apoptosis, was observed upon TRIM32 induction [ 133 ].…”

Section: Trim32 Glucose Metabolism and Link To Cancermentioning

confidence: 99%

TRIM32: A Multifunctional Protein Involved in Muscle Homeostasis, Glucose Metabolism, and Tumorigenesis

2021

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Human tripartite motif family of proteins 32 (TRIM32) is a ubiquitous multifunctional protein that has demonstrated roles in differentiation, muscle physiology and regeneration, and tumor suppression. Mutations in TRIM32 result in two clinically diverse diseases. A mutation in the B-box domain gives rise to Bardet–Biedl syndrome (BBS), a disease whose clinical presentation shares no muscle pathology, while mutations in the NHL (NCL-1, HT2A, LIN-41) repeats of TRIM32 causes limb-girdle muscular dystrophy type 2H (LGMD2H). TRIM32 also functions as a tumor suppressor, but paradoxically is overexpressed in certain types of cancer. Recent evidence supports a role for TRIM32 in glycolytic-mediated cell growth, thus providing a possible mechanism for TRIM32 in the accumulation of cellular biomass during regeneration and tumorigenesis, including in vitro and in vivo approaches, to understand the broad spectrum of TRIM32 functions. A special emphasis is placed on the utility of the Drosophila model, a unique system to study glycolysis and anabolic pathways that contribute to the growth and homeostasis of both normal and tumor tissues.

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“…As a tumor suppressor, TRIM32 mediates degradation of the anti-apoptotic protein XIAP which finally enhances the sensitivity towards anti-cancer drugs and of MYCN, a protein that controls asymmetric division of neuroblastoma cells [ 298 , 299 ]. TRIM32 is frequently upregulated in breast cancer, skin cancer, head and neck cancer and non-small lung cancer [ 117 , 267 , 268 , 269 ]. Also, TRIM59 is highly upregulated in breast, colorectal, gastric and pancreatic cancer and in several breast cancer and colorectal cancer cell lines, and this upregulation is correlated with lymph node metastasis in breast cancer and with poor prognosis for patients [ 78 , 270 , 271 , 272 ].…”

Section: E3s and Tumorigenesismentioning

confidence: 99%

Regulation of p53 by E3s

Pan

Blattner

2021

Cancers

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More than 40 years of research on p53 have given us tremendous knowledge about this protein. Today we know that p53 plays a role in different biological processes such as proliferation, invasion, pluripotency, metabolism, cell cycle control, ROS (reactive oxygen species) production, apoptosis, inflammation and autophagy. In the nucleus, p53 functions as a bona-fide transcription factor which activates and represses transcription of a number of target genes. In the cytoplasm, p53 can interact with proteins of the apoptotic machinery and by this also induces cell death. Despite being so important for the fate of the cell, expression levels of p53 are kept low in unstressed cells and the protein is largely inactive. The reason for the low expression level is that p53 is efficiently degraded by the ubiquitin-proteasome system and the vast inactivity of the tumor suppressor protein under normal growth conditions is due to the absence of activating and the presence of inactivating posttranslational modifications. E3s are important enzymes for these processes as they decorate p53 with ubiquitin and small ubiquitin-like proteins and by this control p53 degradation, stability and its subcellular localization. In this review, we provide an overview about E3s that target p53 and discuss the connection between p53, E3s and tumorigenesis.

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TRIM32 overexpression improves chemoresistance through regulation of mitochondrial function in non-small-cell lung cancers

Cited by 16 publications

References 26 publications

Inhibition of TRIM32 Attenuates the Apoptosis, Oxidative Stress and Inflammatory Injury of Podocytes Induced by High Glucose by Affecting the Akt/GSK-3β/Nrf2 Pathway

Inhibition of TRIM32 Attenuates the Apoptosis, Oxidative Stress and Inflammatory Injury of Podocytes Induced by High Glucose by Affecting the Akt/GSK-3β/Nrf2 Pathway

TRIM32: A Multifunctional Protein Involved in Muscle Homeostasis, Glucose Metabolism, and Tumorigenesis

Regulation of p53 by E3s

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