HIF-1α Induces HECTD2 Up-Regulation and Aggravates the Malignant Progression of Renal Cell Cancer via Repressing miR-320a

Lv, Dong; Shen, Taimin; Yao, Juncheng; Yang, Qi; Xiang, Ying; Ma, Zhiwei

doi:10.3389/fcell.2021.775642

Cited by 9 publications

(4 citation statements)

References 50 publications

(44 reference statements)

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“…In colorectal cancer cells, HECTD2 overexpression induces LPCAT1 ubiquitination and degradation, inhibiting tumor cell proliferation (28). In RCC cells, by weakening miR-320a, HIF-1α increases the expression of HECTD2, boosting tumor cell proliferation, migration, invasion, and EMT while decreasing apoptosis and hastening the malignant development of cancer cells (29). We saw up-regulated HECTD2 in RCC through clinical analysis, which is consistent with previous research.…”

Section: Discussionsupporting

confidence: 90%

HECTD2/TNFAIP1 Axis Regulating the p38/JNK Pathway to Promote an Inflammatory Response in Renal Cell Carcinoma Cells

LV,

CHEN,

TANG

et al. 2024

In Vivo

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Background/Aim: The underlying processes of renal cell carcinoma (RCC), one of the deadliest malignancies of the urinary system, are still poorly understood. HECT domain E3 ubiquitin protein ligase 2 (HECTD2) is an E3 ubiquitin ligase implicated in the pulmonary inflammatory response. This study investigated the impact of HECTD2 on regulating inflammation in RCC cells and its potential mechanisms. Materials and Methods: HECTD2 expression in RCC tissues was examined. Immunoprecipitation and western blot (WB) analysis confirmed that HECTD2 up-regulated euchromatic histone lysine methyltransferase 2 (EHMT2) protein degradation. ChIP experiments validated tumor necrosis factor α Inducing protein 1 (TNFAIP1) as a direct target of EHMT2. qRT-PCR determined HECTD2 and TNFAIP1 expression in RCC cells. Cell viability was assayed via CCK-8. ELISA was employed to measure the expression of . WB analysis was conducted to test p38/JNK pathway-related protein (p38, p-p38, JNK, and p-JNK) expression. Results: HECTD2 and TNFAIP1 were significantly up-regulated in RCC patient tissues and cells. Subsequent investigations revealed that HECTD2 promoted an inflammatory response in RCC cells. Additionally, HECTD2 upregulated TNFAIP1 expression, and high TNFAIP1 expression could reverse the repressive impact of low HECTD2 expression on the inflammatory response in RCC cells. Rescue experiments demonstrated that the addition of p38/JNK pathway inhibitors attenuated the impact of TNFAIP1 overexpression on the RCC inflammatory response. Conclusion: Our findings establish a new mechanism by which HECTD2 exerts a pro-inflammatory role in RCC cells and present a prospective method for an antiinflammatory intervention targeting the HECTD2/TNFAIP1 axis in malignancies.One of the most prevalent malignancies of the genitourinary system, renal cell carcinoma (RCC), has a significant death rate (1). A prevalent subtype of RCC, clear cell RCC (ccRCC), accounts for around 75% of RCC cases (2, 3). Due to high rates of RCC recurrence and metastasis, the prognosis for patients is still dismal despite advances in medical technology (3). Therefore, it is necessary to dissect molecular regulatory mechanisms underlying RCC development and identify new biomarkers for targeted therapy.In recent years, the association between inflammation and cancer has become a focus of cancer research. Inflammation is a fundamental innate immune response of the body to disrupted tissue homeostasis (4). Inflammatory molecules have a crucial role in the development of several malignancies, including breast, lung, colon cancer and RCC, as shown by numerous studies (5-8). For instance, the inflammasome adaptor protein PYCARD is a protein involved in inflammation, pyroptosis, and apoptosis. The expression of PYCARD is associated with immune response and its overexpression is positively correlated with poor prognosis in ccRCC patients (9). This study aimed to further explore the mechanisms influencing inflammatory response in RCC cells and provide new directions for the treatment ...

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Section: Discussionsupporting

confidence: 90%

HECTD2/TNFAIP1 Axis Regulating the p38/JNK Pathway to Promote an Inflammatory Response in Renal Cell Carcinoma Cells

LV,

CHEN,

TANG

et al. 2024

In Vivo

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“… 36 More recent data revealed that HIF-1α could upregulate HECT domain E3 ubiquitin-protein ligase 2, a target gene of miR-320a, in renal cells. 37 Preliminary results in our study indicated that lncNEAT1 and HIF-1α could competitively bind to miR-320a, and lncNEAT1 could upregulate HIF-1α expression by inhibiting miR-320a. Therefore, we further speculated that lncNEAT1/miR-320a might act as a ceRNA network to jointly regulate HIF-1α and affect the invasion, migration and permeability of ARPE-19 cells.…”

Section: Discussionmentioning

confidence: 57%

Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1α Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy

Zhu

Cheng

Kuang

2023

Invest. Ophthalmol. Vis. Sci.

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Purpose To determine the mechanism that long noncoding RNA NEAT1 (lncNEAT1)/miR-320a competitive endogenous RNA (ceRNA) network regulates hypoxia-inducible factor–1α (HIF-1α) in ARPE-19 cells and its potential role in diabetic retinopathy (DR). Methods ARPE-19 cells were cultured in a normal or high-glucose (HG) medium, and cell migration, invasion, and permeability were detected by scratch, transwell, and FITC-dextran staining assays. LncNEAT1, HIF-1α, ZO-1, occludin, N-cadherin, and vimentin levels were tested. The binding of lncNEAT1 to miR-320a was verified by dual-luciferase reporter assay, and the binding of miR-320a to HIF-1α by RIP assay. ARPE-19 cells were treated with lncNEAT1 or HIF-1α shRNA or miR-320a agomir to determine the activation of ANGPTL4/p-STAT3 pathway. The effect of lncNEAT1 in DR and its regulations on miR-320a and HIF-1α were determined in a rat model of DR. Results HG treatment promoted the migration, invasion, and permeability of ARPE-19 cells. After lncNEAT1 silencing, HIF-1α, N-cadherin, and vimentin levels were downregulated, ZO-1 and occludin levels were upregulated, and the migration, permeability, and invasion of HG-treated ARPE-19 cells were inhibited. However, HIF-1α overexpression increased N-cadherin and vimentin expression, reduced ZO-1 and occludin expression, and promoted the migration, permeability, and invasion of ARPE-19 cells. The binding of miR-320a with both lncNEAT1 and HIF-1α was predicted and confirmed. In a diabetic rat model, silencing lncNEAT1 inhibited HIF-1α/ANGPTL4/p-STAT3 pathway activation and alleviated retinopathy. Conclusions The lncNETA1/miR-320a/HIF-1α ceRNA network activates the ANGPTL4/p-STAT3 pathway and promotes HG-induced ARPE-19 cell invasion and migration.

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“…KEGG analysis showed that DEGs were mainly enriched in the HIF-1 signaling pathway, glycolysis/gluconeogenesis signaling pathway, COVID-19 signaling pathway, and ribosome-related signaling pathway. It has been demonstrated that HIF-1 can hinder miR-32's upregulation of HECTD2, hence accelerating the progression of renal carcinoma (Lv et al, 2021). A poor prognosis is typically predicted by elevated HIF1 in ccRCC (Gudas et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

A new CCCH-type zinc finger-related lncRNA signature predicts the prognosis of clear cell renal cell carcinoma patients

Shen

Chen²,

Jiang³

et al. 2022

Front. Genet.

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Background: Clear cell renal cell carcinoma (ccRCC) is the main component of renal cell carcinoma (RCC), and advanced ccRCC frequently indicates a poor prognosis. The significance of the CCCH-type zinc finger (CTZF) gene in cancer has been increasingly demonstrated during the past few years. According to studies, targeted radical therapy for cancer treatment may be a revolutionary therapeutic approach. Both lncRNAs and CCCH-type zinc finger genes are essential in ccRCC. However, the predictive role of long non-coding RNA (lncRNA) associated with the CCCH-type zinc finger gene in ccRCC needs further elucidation. This study aims to predict patient prognosis and investigate the immunological profile of ccRCC patients using CCCH-type zinc finger-associated lncRNAs (CTZFLs).Methods: From the Cancer Genome Atlas database, RNA-seq and corresponding clinical and prognostic data of ccRCC patients were downloaded. Univariate and multivariate Cox regression analyses were conducted to acquire CTZFLs for constructing prediction models. The risk model was verified using receiver operating characteristic curve analysis. The Kaplan-Meier method was used to analyze the overall survival (OS) of high-risk and low-risk groups. Multivariate Cox and stratified analyses were used to assess the prognostic value of the predictive feature in the entire cohort and different subgroups. In addition, the relationship between risk scores, immunological status, and treatment response was studied.Results: We constructed a signature consisting of eight CTZFLs (LINC02100, AC002451.1, DBH-AS1, AC105105.3, AL357140.2, LINC00460, DLGAP1-AS2, AL162377.1). The results demonstrated that the prognosis of ccRCC patients was independently predicted by CTZFLs signature and that the prognosis of high-risk groups was poorer than that of the lower group. CTZFLs markers had the highest diagnostic adequacy compared to single clinicopathologic factors, and their AUC (area under the receiver operating characteristic curve) was 0.806. The overall survival of high-risk groups was shorter than that of low-risk groups when patients were divided into groups based on several clinicopathologic factors. There were substantial differences in immunological function, immune cell score, and immune checkpoint expression between high- and low-risk groups. Additionally, Four agents, including ABT737, WIKI4, afuresertib, and GNE 317, were more sensitive in the high-risk group.Conclusion: The Eight-CTZFLs prognostic signature may be a helpful prognostic indicator and may help with medication selection for clear cell renal cell carcinoma.

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HIF-1α Induces HECTD2 Up-Regulation and Aggravates the Malignant Progression of Renal Cell Cancer via Repressing miR-320a

Cited by 9 publications

References 50 publications

HECTD2/TNFAIP1 Axis Regulating the p38/JNK Pathway to Promote an Inflammatory Response in Renal Cell Carcinoma Cells

HECTD2/TNFAIP1 Axis Regulating the p38/JNK Pathway to Promote an Inflammatory Response in Renal Cell Carcinoma Cells

Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1α Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy

A new CCCH-type zinc finger-related lncRNA signature predicts the prognosis of clear cell renal cell carcinoma patients

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