FBXO22 inhibits proliferation and metastasis of cervical cancer cells by mediating ubiquitination-dependent degradation of GAK.

Cervical cancer is one of the recognized malignant tumors of female reproductive system. At present, the research and development of biomarkers has attracted increasing attention, and the wide application of clinical cervical cancer screening strategies has significantly reduced its morbidity and mortality. A member of the F-box protein family, FBXO22, is involved in cell cycle, DNA damage repair and many other processes. Dysregulation of FBXO22 plays an important role in the occurrence and development of various tumors, including ovarian cancer, liver cancer and lung cancer. Nevertheless, the effect of FBXO22 in cervical cancer needs further investigation. We found that FBXO22 inhibited cervical cancer cell proliferation, migration and invasion. The results of proteomics studies suggested FBXO22 appears to target the Cyclin G Associated Kinase (GAK) for degradation. The combined results of analysis of cultured cells with altered abundance of FBXO22 by depletion or over-expression in the presence or absence of proteasomal inhibitor, comparison of protein decay rate, as well as cellular ubiquitination, support a hypothesis that FBXO22 mediates the ubiquitin-dependent degradation of GAK. Taken together, our data suggest that FBXO22 has a protective role in cervical cancer.

Expanding uncapped translation and emerging function of circular RNA in carcinomas and noncarcinomas.

Circular RNAs (circRNAs) are classified as noncoding RNAs because they are devoid of a 5' end cap and a 3' end poly (A) tail necessary for cap-dependent translation. However, increasing numbers of translated circRNAs identified through high-throughput RNA sequencing overlapping with polysome profiling indicate that this rule is being broken. CircRNAs can be translated in cap-independent mechanism, including IRES (internal ribosome entry site)-initiated pattern, MIRES (m6A internal ribosome entry site) -initiated patterns, and rolling translation mechanism (RCA). CircRNA-encoded proteins harbour diverse functions similar to or different from host proteins. In addition, they are linked to the modulation of human disease including carcinomas and noncarcinomas. CircRNA-related translatomics and proteomics have attracted increasing attention. This review discusses the progress and exclusive characteristics of circRNA translation and highlights the latest mechanisms and regulation of circRNA translatomics. Furthermore, we summarize the extensive functions and mechanisms of circRNA-derived proteins in human diseases, which contribute to a better understanding of intricate noncanonical circRNA translatomics and proteomics and their therapeutic potential in human diseases.

DKC1 enhances angiogenesis by promoting HIF-1α transcription and facilitates metastasis in colorectal cancer.

BACKGROUND: Dyskeratosis congenita 1 (DKC1) is dysregulated in several cancers. However, the expression and function of DKC1 in colorectal cancer (CRC) is rarely reported. METHODS: Tissue microarrays (TAMs) including 411 cases of CRC tissues and corresponding paracancerous tissues were used to examine the DKC1 expression. The correlations between the DKC1 expression and clinicopathological or survival characters were further analysed. The functions and molecular mechanism of DKC1 in CRC were investigated through a series of in vitro and in vivo experiments. RESULTS: The result showed that DKC1 expression was increased in CRC tissues. Increased DKC1 expression was associated with high grade of TNM stage, additional lymph node metastasis, and poor prognosis of patients with CRC. Multivariate COX analysis indicated that DKC1 can act as an independent prognostic factor for patients with CRC. DKC1 also facilitated the CRC angiogenesis and metastasis by increasing HIF-1α and VEGF expression levels. Chromatin immunoprecipitation assay demonstrated that DKC1 facilitated HIF-1α expression by regulating HIF-1α promoter activity. CONCLUSION: DKC1 appears to regulate CRC angiogenesis and metastasis through directly activating HIF-1α transcription. DKC1 can serve as an accurate indicator in predicting the prognosis of patients with CRC and act as a potential therapeutic target for CRC.

The kinesin motor protein KIF4A as a potential therapeutic target in renal cell carcinoma.

Kinesin family member 4A (KIF4A) is located in the human chromosome band Xq13.1. It has a highly conserved kinesin motor region at its N-terminus, which is followed by a central coiled-coil region and a C-terminus cargo-binding domain that contains a cysteine-rich motif. It is aberrantly expressed in a variety of cancers. Our study aimed to determine the expression of KIF4A in renal cell carcinoma (RCC) and to gain new insights into the underlying molecular mechanisms of this disease. Here, we found that KIF4A expression in RCC specimens increased relative to that in normal renal tissues. A significant correlation existed between the expression of KIF4A and the clinicopathologic features of RCC. Elevated KIF4A expression was associated with poor overall survival and disease-free survival. Univariate and multivariate Cox regression analysis revealed that KIF4A was an independent prognostic factor for poor survival in human patients with RCC. CCK-8 proliferation assay, cell cycle analysis, and subcutaneous tumor formation analysis in nude mice consistently showed that KIF4A promoted RCC proliferation. Our findings also indicated that KIF4A functions as an accelerator of RCC metastasis as certified through transwell chamber analysis, wound healing assay, and angiogenesis assay. The expression levels of cyclin D1, cyclin E2, matrix metalloproteinase-2, matrix metalloproteinase-9, hypoxia-inducible factor 1α, and vascular endothelial growth factor in the KIF4A knockdown group were lower than those in the control group and were consistent with those in classic oncogenic pathways. These findings implied that the expression of KIF4A was significantly related to the tumor incidence, metastasis, and prognosis of patients with RCC. Our work provides new breakthroughs for the diagnosis and treatment of RCC.

Functional roles of circular RNAs during epithelial-to-mesenchymal transition.

Cancer has become a major health issue worldwide, contributing to a high mortality rate. Tumor metastasis is attributed to the death of most patients. Epithelial-to-mesenchymal transition (EMT) plays a vital role in inducing metastasis. During EMT, epithelial cells lose their characteristics, such as cell-to-cell adhesion and cell polarity, and cells gain motility, migratory potential, and invasive properties to become mesenchymal stem cells. Circular RNAs (circRNAs) are closely associated with tumor metastasis and patient prognosis, as revealed by increasing lines of evidence. CircRNA is a type of single-stranded RNA that forms a covalently closed continuous loop. CircRNAs are insensitive to ribonucleases and are widespread in body fluids. This work is the first review on EMT-related circRNAs. In this review, we briefly discuss the characteristics and functions of circRNAs. The correlation of circRNAs with EMT has been reported, and we discuss the ways circRNAs can regulate EMT progression through EMT transcription factors, EMT-related signaling pathways, and other mechanisms. This work summarizes current studies on EMT-related circRNAs in various cancers and provides a theoretical basis for the use of EMT-related circRNAs in targeted management and therapy.

PinX1 represses renal cancer angiogenesis via the mir-125a-3p/VEGF signaling pathway.

BACKGROUND: PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a tumor suppressor in various tumors. However, the molecular mechanism underlying PinX1's role in cancer development and progression remains unclear. In this study, we aimed to uncover the new molecular mechanism and role of PinX1 in renal cell carcinoma (RCC) progression. METHODS: We used miRNA microarray to detect the different expressed miRNAs upon PinX1 knockdown. Chromatin immunoprecipitation and Luciferase reporter assays were taken to identify the molecular mechanism of PinX1 in regulating mir-125-3p. In situ hybridization was performed to analyze the expression of mir-125a-3p in RCC using tissue microarray. The correlations between the mir-125a-3p expression level and clinicopathological features were evaluated using the χ2 test. The role and molecular mechanism of PinX1 in RCC angiogenesis were investigated through a series of in vitro and in vivo experiments. RESULTS: In this study, we discovered a new molecular mechanism of PinX1, in which PinX1 transcriptionally activated mir-125a-3p expression, thereby inhibiting the expression of vascular endothelial growth factor (VEGF), which is the target gene of mir-125a-3p. PinX1 also repressed tumor angiogenesis by increasing the mir-125a-3p expression in renal cancer. Moreover, the loss of mir-125a-3p expression was manifested in patients with RCC, and low miR-125a-3p levels correlated with poor survival of these patients. CONCLUSIONS: PinX1 represses renal cancer angiogenesis through mir-125a-3p/VEGF signal pathway. The miR-125a-3p may be a candidate clinical prognostic marker and a novel therapeutic target in RCC.

Polypyrimidine tract-binding protein 3/insulin-like growth factor 2 mRNA-binding proteins 3/high-mobility group A1 axis promotes renal cancer growth and metastasis.

Polypyrimidine tract-binding protein 3 (PTBP3) plays an important role in the post-transcriptional regulation of gene expression, including mRNA splicing, translation, and stability. Increasing evidence has shown that PTBP3 promotes cancer progression in several tumor types. However, the molecular mechanisms of PTBP3 in renal cell carcinoma (RCC) remain unknown. Here, tissue microarrays (TMAs) suggested that PTBP3 expression was increased in human RCC and that high PTBP3 expression was correlated with poor five-year overall survival and disease-free survival. We also showed that PTBP3 binds with HMGA1 mRNA in the 3'UTR region and let-7 miRNAs. PTBP3 interacted with IGF2BP3, and the PTBP3/IGF2BP3 axis prevented let-7 mediated HMGA1 mRNA silencing. PTBP3 promotes renal cancer cell growth and metastasis in vitro and in vivo. Taken together, our findings indicate PTBP3 serves as a regulator of HMGA1 and suggest its potential as a therapeutic agent for RCC.

Phosphorylated FOXQ1, a novel substrate of JNK1, inhibits sorafenib-induced ferroptosis by activating ETHE1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant cancer with poor overall survival. The application of sorafenib is a major breakthrough in the treatment of HCC. In our study, FOXQ1 was significantly overexpressed in sorafenib-resistant HCC cells and suppressed sorafenib-induced ferroptosis. We found that phosphorylation of FOXQ1 at serine 248 is critical for the suppression of sorafenib-induced ferroptosis. Furthermore, as the upstream phosphorylation kinase of FOXQ1, JNK1, which is activated by sorafenib, can directly phosphorylate the serine 248 site of FOXQ1. Then, the phosphorylated FOXQ1 got a high affinity for the promoter of ETHE1 and activates its transcription. Further flow cytometry results showed that ETHE1 reduced intracellular lipid peroxidation and iron levels. Collectively, our study implicated the JNK1-FOXQ1-ETHE1 axis in HCC ferroptosis induced by sorafenib, providing mechanistic insight into sensitivity to sorafenib therapy of HCC.

FBXO22 promotes glioblastoma malignant progression by mediating VHL ubiquitination and degradation.

Glioblastoma (GBM) is the most common malignant primary brain tumor. Despite comprehensive treatment with traditional surgery, radiotherapy, and chemotherapy, the median survival rate is <14.6% and the 5-year survival rate is only 5%. FBXO22, a substrate receptor of the SCF ubiquitin ligases, has been reported to play a promoting role in melanoma, liver cancer, cervical cancer, and other cancers. However, the function of FBXO22 in GBM has not been reported. In the present study, we demonstrate that FBXO22 is highly expressed in glioma and is positively correlated with worse pathological features and shorter survival of GBM patients. We revealed that FBXO22 promotes GBM cell proliferation, angiogenesis, migration, and tumorigenesis in vitro and in vivo. In terms of mechanism, we reveal that FBXO22 decreases VHL expression by directly mediating VHL ubiquitination degradation, which ultimately increases HIF-1α and VEGFA expression. In addition, our data confirm that there are positive correlations among FBXO22, HIF-1α, and VEGFA expression, and there is a negative correlation between FBXO22 and VHL protein expression in glioma patients. Our study strongly indicates that FBXO22 is a promising diagnostic marker and therapeutic target for glioma patients.

circEPB41L2 blocks the progression and metastasis in non-small cell lung cancer by promoting TRIP12-triggered PTBP1 ubiquitylation.

The metastasis of non-small cell lung cancer (NSCLC) is the leading death cause of NSCLC patients, which requires new biomarkers for precise diagnosis and treatment. Circular RNAs (circRNAs), the novel noncoding RNA, participate in the progression of various cancers as microRNA or protein sponges. We revealed the mechanism by which circEPB41L2 (hsa_circ_0077837) blocks the aerobic glycolysis, progression and metastasis of NSCLC through modulating protein metabolism of PTBP1 by the E3 ubiquitin ligase TRIP12. With ribosomal RNA-depleted RNA seq, 57 upregulated and 327 downregulated circRNAs were identified in LUAD tissues. circEPB41L2 was selected due to its dramatically reduced levels in NSCLC tissues and NSCLC cells. Interestingly, circEPB41L2 blocked glucose uptake, lactate production, NSCLC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, acting as a scaffold, circEPB41L2 bound to the RRM1 domain of the PTBP1 and the E3 ubiquitin ligase TRIP12 to promote TRIP12-mediated PTBP1 polyubiquitylation and degradation, which could be reversed by the HECT domain mutation of TRIP12 and circEPB41L2 depletion. As a result, circEPB41L2-induced PTBP1 inhibition led to PTBP1-induced PKM2 and Vimentin activation but PKM1 and E-cadherin inactivation. These findings highlight the circEPB41L2-dependent mechanism that modulates the "Warburg Effect" and EMT to inhibit NSCLC development and metastasis, offering an inhibitory target for NSCLC treatment.

The role of transcription factor Yin Yang-1 in colorectal cancer.

BACKGROUND: Yin Yang-1 (YY1) is identified as a transcription factor with multiple functions. However, the role of YY1 in tumorigenesis remains controversial and its regulatory effects may depend upon not only cancer types, but also its interacting partners, chromatin structure, and the context in which it acts. It has been detected that YY1 was highly expressed in colorectal cancer (CRC). Intriguingly, many YY1-repressed genes exhibit tumor suppressive potential while YY1 silencing is related to chemotherapy resistance. Therefore, it is crucial to meticulously explore YY1 protein structure and the dynamic alteration of its interactome in each cancer type. This review attempts to describe the structure of YY1, summarize the mechanism that influence the expression level of YY1 and also highlight the recent advances in our understanding of regulatory insights of YY1 functions in CRC. METHODS: Related studies were identified through scoping search of PubMed, Web of science, Scopus and Emhase concerning the terms of "colorectal cancer", colorectal carcinoma" or CRC with "YY1". The retrieval strategy included title, abstract, and keywords with no language limitations. All the included articles were categorized depending on the mechanisms they explored. RESULTS: In total, 170 articles were identified for further screening. After removing the duplication, not relevant outcomes and review articles, 34 were finally included in the review. Among them, 10 articles revealed the reasons of YY1 high expression in CRC, 13 articles explored YY1 function in CRC, and 11 articles fell into both aspects. In addition, we also summarized 10 clinical trials concerning the expression and activity of YY1 in various diseases, which offers a hint for future application. CONCLUSIONS: YY1 is highly expressed in CRC and broadly recognized as an oncogenic factor during the whole course of CRC. Sporadic controversial views are raised in term of CRC treatment, reminding us that future studies should take the influence of therapeutic regimens into concern.

PRMT2 promotes RCC tumorigenesis and metastasis via enhancing WNT5A transcriptional expression.

Protein arginine methyltransferase 2 (PRMT2) is involved in several biological processes via histone methylation and transcriptional regulation. Although PRMT2 has been reported to affect breast cancer and glioblastoma progression, its role in renal cell cancer (RCC) remains unclear. Here, we found that PRMT2 was upregulated in primary RCC and RCC cell lines. We demonstrated that PRMT2 overexpression promoted RCC cell proliferation and motility both in vitro and in vivo. Moreover, we revealed that PRMT2-mediated H3R8 asymmetric dimethylation (H3R8me2a) was enriched in the WNT5A promoter region and enhanced WNT5A transcriptional expression, leading to activation of Wnt signaling and malignant progression of RCC. Finally, we confirmed that high PRMT2 and WNT5A expression was strongly correlated with poor clinicopathological characteristics and poor overall survival in RCC patient tissues. Our findings indicate that PRMT2 and WNT5A may be promising predictive diagnostic biomarkers for RCC metastasis. Our study also suggests that PRMT2 is a novel therapeutic target in patients with RCC.

TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability.

BACKGROUND: Metabolic reprogramming is a hallmark of various cancers. Targeting metabolic processes is a very attractive treatment for cancer. Renal cell carcinoma (RCC) is a type of metabolic disease, and the lipidomic profile of RCC is significantly altered compared with that of healthy tissue. However, the molecular mechanism underlying lipid metabolism regulation in RCC is not clear. METHODS: The XF long-chain fatty acid oxidative stress test kits were used to assess the dependence on long-chain fatty acids and mitochondrial function after knockdown TRIM21 in RCC cells. The effect of TRIM21 on the lipid content in RCC cells was determined by metabolomics analysis, Oil Red O staining, and cellular Nile red staining. qRT-PCR and western blot were used to explore the relationship between TRIM21 and lipogenesis, and then the key molecule sterol regulatory element binding transcription factor 1 (SREBF1) was identified to interact with TRIM21 by immunoprecipitation, which was also identified in an orthotopic model. Subsequently, the relevance and clinical significance of TRIM21 and SREBF1 were analyzed by The Cancer Genome Atlas (TCGA) database, and 239 tissues were collected from RCC patients. RESULTS: TRIM21 silencing attenuated the dependence of RCC cells on fatty acids, and enhanced lipid accumulation in RCC cells. TRIM21 overexpression significantly decreased lipid contents by decreasing the expression of lipogenic enzymes via ubiquitination-mediated degradation of SREBF1. SREBF1 is critical for TRIM21-mediated lipogenesis inhibition in vitro and in vivo. Moreover, TRIM21 expression is negatively correlated with SREBF1 expression, and TRIM21-SREBF1 is a reliable combinational biomarker for RCC prognosis. CONCLUSION: The findings from this study reveal a novel pathway through which TRIM21 inhibits the lipid metabolism process of RCC and shed light on the development of targeted metabolic treatment and prognosis diagnosis of RCC.

Long noncoding RNA SH3PXD2A-AS1 promotes NSCLC proliferation and accelerates cell cycle progression by interacting with DHX9.

As the most commonly diagnosed lung cancer, non-small cell lung carcinoma (NSCLC) is regulated by many long noncoding RNAs (lncRNAs). In the present study, we found that SH3PXD2A-AS1 expression in NSCLC tissues was upregulated compared with that in normal lung tissues in The Cancer Genome Atlas (TCGA) database by using the GEPIA website. K-M analysis was performed to explore the effects of this molecule on the survival rate in NSCLC. The results demonstrated that SH3PXD2A-AS1 expression was increased in human NSCLC, and high SH3PXD2A-AS1 expression was correlated with poor overall survival. SH3PXD2A-AS1 promotes lung cancer cell proliferation and accelerates cell cycle progression in vitro. Animal studies validated that knockdown of SH3PXD2A-AS1 inhibits NSCLC cell proliferation in vivo. Mechanically, SH3PXD2A-AS1 interacted with DHX9 to enhance FOXM1 expression, promote tumour cell proliferation and accelerate cell cycle progression. Altogether, SH3PXD2A-AS1 promoted NSCLC growth by interacting with DHX9 to enhance FOXM1 expression. SH3PXD2A-AS1 may serve as a promising predictive biomarker for the diagnosis and prognosis of patients with NSCLC.

KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells.

Glioma is one of the most prevalent cancers diseases in the worldwide. Kinesin superfamily protein 4 (KIF4), a KIF member classified in Kinesin 4 has been indicated as a mediator acted in tumorigenesis of human cancer. However, the mechanism of KIF4A on glioma is yet to be investigated. This study aimed to explore the potential function and mechanism of KIF4A in gliomas. We analyzed the KIF4A expression and the prognosis in gliomas patients using The Cancer Genome Atlas (TCGA) databases. KIF4A level in normal human astrocyte cell (NHA) and glioma cell lines were examined by Western blot. We studied the function of KIF4A on proliferation, migration, invasion, cell cycle in glioma cell lines using a series of in vitro and in vivo experiments. Chromatin Immunoprecipitation (ChIP) analysis was applied to searching potential KIF4A related downstream in glioma. We identified the significant up-regulated expression of KIF4A both in glioma tissues and cell. Glioma patients with elevated KIF4A expression have shorter survival. Down-regulation of KIF4A exerted inhibitory effect on cell proliferation, invasion and migration. We crucially identified that KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. Knockdown of KIF4A decreased RohA, Rac1, Cdc42, Pak1 and Pak2 expression level. Our study provided a prospect that KIF4A functions as an oncogene in glioma.

DNMT1-mediated epigenetic silencing of TRAF6 promotes prostate cancer tumorigenesis and metastasis by enhancing EZH2 stability.

A plethora of studies have shown that both DNMT1 and EZH2 have great effects on the progression of a variety of cancers. However, it remains unclear whether the expression profiles of these two epigenetic enzymes are molecularly intertwined in prostate cancer (PC), especially in castration-resistant prostate cancer (CRPC). Here, we found that DNMT1 is highly expressed and facilitates PC cell proliferation and migration. Importantly, we demonstrate that the abrogation of DNMT1 expression can induce the decreased expression of EZH2, resulting in the less aggressive capacity of PC cells. Mechanistically, we discovered that DNMT1 promotes PC tumorigenesis and metastasis by inhibiting TRAF6 transcriptional expression and subsequent TRAF6-mediated EZH2 ubiquitination. Finally, we confirmed that there is a negative correlation between DNMT1 and TRAF6 expression and a positive correlation between DNMT1 and EZH2 expression in PC patients. In this study, we first disclose that there is a direct crosstalk between DNA methyltransferase DNMT1 expression and histone methyltransferase EZH2 expression in tumorigenesis and cancer metastasis in vitro and in vivo. Our results also show that targeting DNMT1 with its inhibitor decitabine (an FDA-approved drug) is an appealing treatment strategy for CRPC patients through epigenetic suppression of both DNMT1-mediated DNA methylation and EZH2-modulated histone methylation.

Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation.

Transketolase (TKT) which is an important metabolic enzyme in the pentose phosphate pathway (PPP) participates in maintaining ribose 5-phosphate levels. TKT is necessary for maintaining cell growth. However, we found that in addition to this, TKT can also affect tumor progression through other ways. Our previous study indicate that TKT could promote the development of liver cancer by affecting bile acid metabolism. And in this study, we discovered that TKT expression was remarkably upregulated in colorectal cancer, abnormal high expression of TKT is associated with poor prognosis of colorectal cancer. Additionally, TKT promoted colorectal cancer cell growth and metastasis. Further study demonstrated that TKT interacted with GRP78 and promoted colorectal cancer cell glycolysis through increasing AKT phosphorylation, thereby enhancing colorectal cancer cell metastasis. Thus, TKT is expected to become an indicator for judging the prognosis of colorectal cancer, and provide a theoretical basis for drug development of new treatment targets for colorectal cancer.

LncRNA LINC00460 facilitates the proliferation and metastasis of renal cell carcinoma via PI3K/AKT signaling pathway.

Renal cell carcinoma (RCC) is one of the most prevalent cancers diseases in the worldwide. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. LINC00460 has been reported to participate in many kinds of malignancies and promotes cancer progressions. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to explore the potential function and regulation mechanism of LINC00460 in RCC. We analysed the LINC00460 expression and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases. LINC00460 level in normal renal cell line and RCC cell lines were examined by qRT-PCR. We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of in vivo and in vitro experiments. RNA sequencing (RNA-seq) analysis was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression of LINC00460 both in RCC tissues and cell. RCC patients with elevated LINC00460 expression have shorter survival. Up-expression of LINC00460 promoted cell proliferation, invasion and migration, meanwhile down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study showed that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT.

The emerging roles of TRIM21 in coordinating cancer metabolism, immunity and cancer treatment.

Tripartite motif containing-21 (TRIM21), an E3 ubiquitin ligase, was initially found to be involved in antiviral responses and autoimmune diseases. Recently studies have reported that TRIM21 plays a dual role in cancer promoting and suppressing in the occurrence and development of various cancers. Despite the fact that TRIM21 has effects on multiple metabolic processes, inflammatory responses and the efficacy of tumor therapy, there has been no systematic review of these topics. Herein, we discuss the emerging role and function of TRIM21 in cancer metabolism, immunity, especially the immune response to inflammation associated with tumorigenesis, and also the cancer treatment, hoping to shine a light on the great potential of targeting TRIM21 as a therapeutic target.