US oil and gas system emissions from nearly one million aerial site measurements.

As airborne methane surveys of oil and gas systems continue to discover large emissions that are missing from official estimates1-4, the true scope of methane emissions from energy production has yet to be quantified. We integrate approximately one million aerial site measurements into regional emissions inventories for six regions in the USA, comprising 52% of onshore oil and 29% of gas production over 15 aerial campaigns. We construct complete emissions distributions for each, employing empirically grounded simulations to estimate small emissions. Total estimated emissions range from 0.75% (95% confidence interval (CI) 0.65%, 0.84%) of covered natural gas production in a high-productivity, gas-rich region to 9.63% (95% CI 9.04%, 10.39%) in a rapidly expanding, oil-focused region. The six-region weighted average is 2.95% (95% CI 2.79%, 3.14%), or roughly three times the national government inventory estimate5. Only 0.05-1.66% of well sites contribute the majority (50-79%) of well site emissions in 11 out of 15 surveys. Ancillary midstream facilities, including pipelines, contribute 18-57% of estimated regional emissions, similarly concentrated in a small number of point sources. Together, the emissions quantified here represent an annual loss of roughly US$1 billion in commercial gas value and a US$9.3 billion annual social cost6. Repeated, comprehensive, regional remote-sensing surveys offer a path to detect these low-frequency, high-consequence emissions for rapid mitigation, incorporation into official emissions inventories and a clear-eyed assessment of the most effective emission-finding technologies for a given region.

Temporal Variation and Persistence of Methane Emissions from Shallow Water Oil and Gas Production in the Gulf of Mexico.

Methane emissions from the oil and gas supply chain can be intermittent, posing challenges for monitoring and mitigation efforts. This study examines shallow water facilities in the US Gulf of Mexico with repeat atmospheric observations to evaluate temporal variation in site-specific methane emissions. We combine new and previous observations to develop a longitudinal study, spanning from days to months to almost five years, evaluating the emissions behavior of sites over time. We also define and determine the chance of subsequent detection (CSD): the likelihood that an emitting site will be observed emitting again. The average emitting central hub in the Gulf has a 74% CSD at any time interval. Eight facilities contribute 50% of total emissions and are over 80% persistent with a 96% CSD above 100 kg/h and 46% persistent with a 42% CSD above 1000 kg/h, indicating that large emissions are persistent at certain sites. Forward-looking infrared (FLIR) footage shows many of these sites exhibiting cold venting. This suggests that for offshore, a low sampling frequency over large spatial coverage can capture typical site emissions behavior and identify targets for mitigation. We further demonstrate the preliminary use of space-based observations to monitor offshore emissions over time.

In Situ Sampling of NOx Emissions from United States Natural Gas Flares Reveals Heavy-Tail Emission Characteristic.

Natural gas flaring is a common practice employed in many United States (U.S.) oil and gas regions to dispose of gas associated with oil production. Combustion of predominantly hydrocarbon gas results in the production of nitrogen oxides (NOx). Here, we present a large field data set of in situ sampling of real world flares, quantifying flaring NOx production in major U.S. oil production regions: the Bakken, Eagle Ford, and Permian. We find that a single emission factor does not capture the range of the observed NOx emission factors within these regions. For all three regions, the median emission factors fall within the range of four emission factors used by the Texas Commission for Environmental Quality. In the Bakken and Permian, the distribution of emission factors exhibits a heavy tail such that basin-average emission factors are 2-3 times larger than the value employed by the U.S. Environmental Protection Agency. Extrapolation to basin scale emissions using auxiliary satellite assessments of flare volumes indicates that NOx emissions from flares are skewed, with 20%-30% of the flares responsible for 80% of basin-wide flaring NOx emissions. Efforts to reduce flaring volume through alternative gas capture methods would have a larger impact on the NOx oil and gas budget than current inventories indicate.

Excess methane emissions from shallow water platforms elevate the carbon intensity of US Gulf of Mexico oil and gas production.

The Gulf of Mexico is the largest offshore fossil fuel production basin in the United States. Decisions on expanding production in the region legally depend on assessments of the climate impact of new growth. Here, we collect airborne observations and combine them with previous surveys and inventories to estimate the climate impact of current field operations. We evaluate all major on-site greenhouse gas emissions, carbon dioxide (CO2) from combustion, and methane from losses and venting. Using these findings, we estimate the climate impact per unit of energy of produced oil and gas (the carbon intensity). We find high methane emissions (0.60 Tg/y [0.41 to 0.81, 95% confidence interval]) exceeding inventories. This elevates the average CI of the basin to 5.3 g CO2e/MJ [4.1 to 6.7] (100-y horizon) over twice the inventories. The CI across the Gulf varies, with deep water production exhibiting a low CI dominated by combustion emissions (1.1 g CO2e/MJ), while shallow federal and state waters exhibit an extraordinarily high CI (16 and 43 g CO2e/MJ) primarily driven by methane emissions from central hub facilities (intermediaries for gathering and processing). This shows that production in shallow waters, as currently operated, has outsized climate impact. To mitigate these climate impacts, methane emissions in shallow waters must be addressed through efficient flaring instead of venting and repair, refurbishment, or abandonment of poorly maintained infrastructure. We demonstrate an approach to evaluate the CI of fossil fuel production using observations, considering all direct production emissions while allocating to all fossil products.

Single-blind validation of space-based point-source detection and quantification of onshore methane emissions.

Satellites are increasingly seen as a tool for identifying large greenhouse gas point sources for mitigation, but independent verification of satellite performance is needed for acceptance and use by policy makers and stakeholders. We conduct to our knowledge the first single-blind controlled methane release testing of satellite-based methane emissions detection and quantification, with five independent teams analyzing data from one to five satellites each for this desert-based test. Teams correctly identified 71% of all emissions, ranging from 0.20 [0.19, 0.21] metric tons per hour (t/h) to 7.2 [6.8, 7.6] t/h. Three-quarters (75%) of quantified estimates fell within ± 50% of the metered value, comparable to airplane-based remote sensing technologies. The relatively wide-area Sentinel-2 and Landsat 8 satellites detected emissions as low as 1.4 [1.3, 1.5, 95% confidence interval] t/h, while GHGSat's targeted system quantified a 0.20 [0.19, 0.21] t/h emission to within 13%. While the fraction of global methane emissions detectable by satellite remains unknown, we estimate that satellite networks could see 19-89% of total oil and natural gas system emissions detected in a recent survey of a high-emitting region.

Exosomes in Genitourinary Cancers: Emerging Mediators of Drug Resistance and Promising Biomarkers.

Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy.

Evaluation of eleven kiwifruit genotypes for bicarbonate tolerance and characterization of two tolerance-contrasting genotypes.

Screening bicarbonate-tolerant genotypes is an environmentally-friendly and long-term effective strategy to cope with bicarbonate-induced chlorosis in fruit crops grown on calcareous soils. We investigated eleven genotypes from four kiwifruit species (Actinidia chinensis, A. macrosperma, A. polygama, and A. valvata) for differences in bicarbonate tolerance. We also characterized the physiological and molecular differences in two contrasting genotypes of this group. In the first experiment, bicarbonate-treated plantlets were irrigated with 3.0 g L-1 CaCO3 and 5.04 g L-1 NaHCO3 in peat and perlite medium culture. Based on principal component analysis, weight-based membership function method and cluster analysis, the tested genotypes were classified into three groups: (1) tolerant, including YX, Av-1, Acd, Ap, Av-2, and QM; (2) moderately tolerant, including Av-3, Am, Av-4, and HWD; and (3) sensitive, including only QH. In the second experiment, QH (bicarbonate-sensitive) and YX (bicarbonate-tolerant) were grown in sand culture with 4.0 g L-1 CaCO3 and 0.84 g L-1 or 1.26 g L-1 NaHCO3. Compared with QH, YX showed a better ability to take up iron (Fe) by roots and to transport Fe from roots to shoots in the bicarbonate treatments, probably due to a better capacity to protect from oxidative damage and to excrete protons, and a differential expression of genes associated with Fe uptake and translocation, including HA8, IRT1, YSL3 and NRAMP3. The results can facilitate identifying potential resources for bicarbonate tolerance and breeding new rootstocks, and contribute to the elucidation of the bicarbonate tolerance mechanisms in the genus Actinidia.

Methane Emissions from Natural Gas Gathering Pipelines in the Permian Basin.

The rapid reduction of methane emissions, especially from oil and gas (O&G) operations, is a critical part of slowing global warming. However, few studies have attempted to specifically characterize emissions from natural gas gathering pipelines, which tend to be more difficult to monitor on the ground than other forms of O&G infrastructure. In this study, we use methane emission measurements collected from four recent aerial campaigns in the Permian Basin, the most prolific O&G basin in the United States, to estimate a methane emission factor for gathering lines. From each campaign, we calculate an emission factor between 2.7 (+1.9/-1.8, 95% confidence interval) and 10.0 (+6.4/-6.2) Mg of CH4 year-1 km-1, 14-52 times higher than the U.S. Environmental Protection Agency's national estimate for gathering lines and 4-13 times higher than the highest estimate derived from a published ground-based survey of gathering lines. Using Monte Carlo techniques, we demonstrate that aerial data collection allows for a greater sample size than ground-based data collection and therefore more comprehensive identification of emission sources that comprise the heavy tail of methane emissions distributions. Our results suggest that pipeline emissions are underestimated in current inventories and highlight the importance of a large sample size when calculating basinwide pipeline emission factors.

Inefficient and unlit natural gas flares both emit large quantities of methane.

Flaring is widely used by the fossil fuel industry to dispose of natural gas. Industry and governments generally assume that flares remain lit and destroy methane, the predominant component of natural gas, with 98% efficiency. Neither assumption, however, is based on real-world observations. We calculate flare efficiency using airborne sampling across three basins responsible for >80% of US flaring and combine these observations with unlit flare prevalence surveys. We find that both unlit flares and inefficient combustion contribute comparably to ineffective methane destruction, with flares effectively destroying only 91.1% (90.2, 91.8; 95% confidence interval) of methane. This represents a fivefold increase in methane emissions above present assumptions and constitutes 4 to 10% of total US oil and gas methane emissions, highlighting a previously underappreciated methane source and mitigation opportunity.

N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma.

BACKGROUND: Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear. METHODS: RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis. RESULTS: We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment. CONCLUSIONS: Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.

Quantifying Regional Methane Emissions in the New Mexico Permian Basin with a Comprehensive Aerial Survey.

Limiting emissions of climate-warming methane from oil and gas (O&G) is a major opportunity for short-term climate benefits. We deploy a basin-wide airborne survey of O&G extraction and transportation activities in the New Mexico Permian Basin, spanning 35 923 km2, 26 292 active wells, and over 15 000 km of natural gas pipelines using an independently validated hyperspectral methane point source detection and quantification system. The airborne survey repeatedly visited over 90% of the active wells in the survey region throughout October 2018 to January 2020, totaling approximately 98 000 well site visits. We estimate total O&G methane emissions in this area at 194 (+72/-68, 95% CI) metric tonnes per hour (t/h), or 9.4% (+3.5%/-3.3%) of gross gas production. 50% of observed emissions come from large emission sources with persistence-averaged emission rates over 308 kg/h. The fact that a large sample size is required to characterize the heavy tail of the distribution emphasizes the importance of capturing low-probability, high-consequence events through basin-wide surveys when estimating regional O&G methane emissions.

Quantitative global proteome and phosphorylome analyses reveal potential biomarkers in kidney cancer.

Currently, high­throughput quantitative proteomic and transcriptomic approaches have been widely used for exploring the molecular mechanisms and acquiring biomarkers for cancers. Our study aimed to illuminate the multi-dimensional molecular mechanisms underlying renal cell carcinoma (RCC) via investigating the quantitative global proteome and the profile of phosphorylation. A total of 5,428 proteins and 8,632 phosphorylation sites were quantified in RCC tissues, with 709 proteins and 649 phosphorylation sites found to be altered in expression compared with the matched adjacent non­tumor tissues. These differentially expressed proteins were mainly involved in metabolic process terms involving the glycolysis pathway, oxidative phosphorylation and fatty acid metabolism which have been considered to be a potential mechanism of RCC progression. Moreover, phosphorylation analysis indicated that these upregulated phosphorylated proteins are implicated in the glucagon signaling pathway and cholesterol metabolism, while the downregulated phosphorylated proteins were found to be predominantly involved in glycolysis, the pentose phosphate pathway, carbon metabolism and biosynthesis of amino acids. In addition, several new candidate proteins, CD14, MPO, NCF2, SOD2, PARP1, were found to be upregulated and MUT, ACADM, PCK1 were downregulated in RCC. These proteins may be recognized as new biomarkers for RCC. These findings could broaden our insight into the underlying molecular mechanisms of RCC and identify candidate biomarkers for the treatment of RCC.

Identification of a Hypoxia-Related Signature for Predicting Prognosis and the Immune Microenvironment in Bladder Cancer.

Accumulating evidence indicates that hypoxia is highly associated with bladder cancer genesis, progression, and immune microenvironment. Nevertheless, few studies have identified the role of hypoxia-related genes as a prognostic signature in bladder cancer. This study aimed to establish a hypoxia-related signature with high accuracy for prognosis and immune microenvironment prediction in bladder cancer. We obtained expression profiles and clinical information from Gene Expression Omnibus and The Cancer Genome Atlas. Then the univariate Cox regression, random survival forest algorithm, and multivariate Cox regression analysis were conducted to identify the core genes and four hypoxia-related genes (ANXA2, GALK1, COL5A1, and HS3ST1) were selected to construct the signature. Kaplan-Meier survival analysis demonstrated that patients with a low-risk score had a higher disease-specific survival rate (p < 0.0001). The areas under the curve of the signature were 0.829 at 1 year, 0.869 at 3 years, and 0.848 at 5 years, respectively. Additionally, we found this hypoxia-related signature was highly correlated with tumor immune microenvironment and had the potential to predict the efficacy of immunotherapy. In summary, our study developed a hypoxia-related signature, which had high accuracy for prognosis prediction and the potential to guide the immunotherapy for bladder cancer patients.

Complete urethral injury in the penile fracture: a case report and literature review.

Penile fracture is described as a traumatic rupture of the tunica albuginea caused by blunt injury to the erect penis. It usually occurs as a single rupture of the tunica albuginea in one of two corpora cavernosa; a rupture with urethral injury is an extremely rare condition. Although its diagnosis is usually clinical, ultrasound plays an important role in confirming diagnosis and identifying the site of the injury. Here, we presented a case of penile fracture with complete urethral injury. A 43-year-old male was admitted to the hospital because of trauma to the genital and dysuria following sexual intercourse. After admission, the patient was diagnosed with double penile fracture and complete urethral injury after the physical and B-ultrasound examinations. Emergency surgery to remove the hematoma and repair the urethra was performed. The patient recovered smoothly and was discharged on the third day after operation. After two months' follow-up, the patient urinated smoothly and achieved an adequate erection without other complications. In this case, consistent with previous studies, emergency surgery for penile fracture is necessary and can preserve the urethral function and sexual function. In addition, there are two lesions in tunica albuginea in this case, so careful search for the penile shaft during the surgery is important to avoid the missed injuries. This report provides evidence of an uncommon and underreported clinical case.

Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.

Drug options for the life-threatening Cushing's disease are limited, and surgical resection or radiation therapy is not invariably effective. Testicular receptor 4 (TR4) has been identified as a novel drug target to treat Cushing's disease. We built the structure model of TR4 and searched the TR4 antagonist candidate via in silico virtual screening. Bexarotene was identified as an antagonist of TR4 that can directly interact with TR4 ligand binding domain (TR4-LBD) and induces a conformational change in the secondary structure of TR4-LBD. Bexarotene suppressed AtT-20 cell growth, proopiomelanocortin (POMC) expression and adrenocorticotropin (ACTH) secretion. Mechanism dissection revealed that bexarotene could suppress TR4-increased POMC expression via promoting the TR4 translocation from the nucleus to the cytoplasm. This TR4 translocation might then result in reducing the TR4 binding to the TR4 response element (TR4RE) on the 5' promoter region of POMC. Results from in vivo mouse model also revealed that oral bexarotene administration markedly suppressed ACTH-secreting tumour growth, adrenal enlargement and the secretion of ACTH and corticosterone in mice with already established tumours. Together, these results suggest that bexarotene may be developed as a potential novel therapeutic drug to better suppress Cushing's disease.

Oncometabolite L-2-hydroxyglurate directly induces vasculogenic mimicry through PHLDB2 in renal cell carcinoma.

Metabolism reprograming is a hallmark of cancer and plays an important role in tumor progression. The aberrant metabolism in renal cell carcinoma (RCC) leads to accumulation of the oncometabolite L-2-hydroxyglurate (L-2HG). L-2HG has been reported to inhibit the activity of some α-ketoglutarate-dependent dioxygenases such as TET enzymes, which mediate epigenetic alteration, including DNA and histone demethylation. However, the detailed functions of L-2HG in renal cell carcinoma have not been investigated thoroughly. In our study, we found that L-2HG was significantly elevated in tumor tissues compared to adjacent tissues. Furthermore, we demonstrated that L-2HG promoted vasculogenic mimicry (VM) in renal cancer cell lines through reducing the expression of PHLDB2. A mechanism study revealed that activation of the ERK1/2 pathway was involved in L-2HG-induced VM formation. In conclusion, these findings highlighted the pathogenic link between L-2HG and VM and suggested a novel therapeutic target for RCC.

Direct and Bicarbonate-Induced Iron Deficiency Differently Affect Iron Translocation in Kiwifruit Roots.

Bicarbonate-induced iron (Fe) deficiency (+Bic) is frequently observed in kiwifruit orchards, but more research attention has been paid to direct Fe deficiency (-Fe) in plants, including kiwifruit. Here we compared the differences of kiwifruit plants between -Fe and +Bic in: (1) the traits of 57Fe uptake and translocation within plants, (2) Fe forms in roots, and (3) some acidic ions and metabolites in roots. The concentration of 57Fe derived from nutrient solution (57Fedfs) in roots was less reduced in +Bic than -Fe treatment, despite similar decrease in shoots of both treatments. +Bic treatment increased 57Fedfs distribution in fine roots but decreased it in new leaves and stem, thereby displaying the inhibition of 57Fedfs translocation from roots to shoots and from fine roots to xylem of coarse roots. Moreover, +Bic imposition induced the accumulation of water-soluble Fe and apoplastic Fe in roots. However, the opposite was observed in -Fe-treated plants. Additionally, the cell wall Fe and hemicellulose Fe in roots were less reduced by +Bic than -Fe treatment. +Bic treatment also triggered the reduction in H+ extrusion and the accumulation of NH4+, succinic acid, and some amino acids in roots. These results suggest that, contrary to -Fe, +Bic treatment inhibits Fe translocation to shoots by accumulating water-soluble and apoplastic Fe and slowing down the release of hemicellulose Fe in the cell wall in kiwifruit roots, which may be related to the decreased H+ extrusion and the imbalance between C and N metabolisms.

The prognostic value of miRNA-18a-5p in clear cell renal cell carcinoma and its function via the miRNA-18a-5p/HIF1A/PVT1 pathway.

Purpose Clear cell renal cell carcinoma(ccRCC) is the most common type of renal cell carcinoma. While it is curable when detected at an early stage, some patients presented with advanced disease have poor prognosis. We aimed to identify key genes and miRNAs associated with clinical prognosis in ccRCC. Methods The microarray datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were analyzed by using GEO2R. Then, Functional enrichment analysis was performed using the DAVID. A retrospective series of 254 ccRCC patients with complete clinical information was included in this study. Kaplan-Meier analysis and multivariate cox regression analysis were used for prognostic analysis. Wound healing assay and transwell assay were designed to evaluate the migration and invasion ability of ccRCC cell lines. Results miRNA-18a was identified to be related with prognosis of ccRCC by using Kaplan-Meier analysis and multivariate cox regression analysis demonstrated that the prognostic value of miRNA-18a was independent of clinical features. Further studies showed that up-regulation of miRNA-18a had a positive effect on migration and invasion of ccRCC cells. The target gene (HIF1A) of the miRNA-18a was predicted by using the miRPathDB database. The transcription factors of DEGs were identified by using the i-cisTarget. Luckily, HIF1A was found to be one of the transcription factors of DEGs. Among these DEGs, PVT1 may be regulated by HIF1A and be related with prognosis of ccRCC. Finally, validation of miRNA18a/HIF1A/PVT1 pathway was checked via reverse transcription-polymerase chain reaction (RT-PCR) assay in both cell lines and clinical tumor samples. Conclusion Our research revealed that miRNA18a/HIF1A/PVT1 pathway might play a crucial role in ccRCC progression, providing novel insights into understanding of ccRCC molecular mechanisms. Importantly, miRNA-18a could serve as a potential diagnostic biomarker and therapeutic targets for ccRCC patients.

Development and verification of a nomogram for prediction of recurrence-free survival in clear cell renal cell carcinoma.

Nowadays, gene expression profiling has been widely used in screening out prognostic biomarkers in numerous kinds of carcinoma. Our studies attempt to construct a clinical nomogram which combines risk gene signature and clinical features for individual recurrent risk assessment and offer personalized managements for clear cell renal cell carcinoma. A total of 580 differentially expressed genes (DEGs) were identified via microarray. Functional analysis revealed that DEGs are of fundamental importance in ccRCC progression and metastasis. In our study, 338 ccRCC patients were retrospectively analysed and a risk gene signature which composed of 5 genes was obtained from a LASSO Cox regression model. Further analysis revealed that identified risk gene signature could usefully distinguish the patients with poor prognosis in training cohort (hazard ratio [HR] = 3.554, 95% confidence interval [CI] 2.261-7.472, P < .0001, n = 107). Moreover, the prognostic value of this gene-signature was independent of clinical features (P = .002). The efficacy of risk gene signature was verified in both internal and external cohorts. The area under receiver operating characteristic curve of this signature was 0.770, 0.765 and 0.774 in the training, testing and external validation cohorts, respectively. Finally, a nomogram was developed for clinicians and did well in the calibration plots. This nomogram based on risk gene signature and clinical features might provide a practical way for recurrence prediction and facilitating personalized managements of ccRCC patients after surgery.

Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals.

BACKGROUND: Circular RNA (circRNA) is a type of circular endogenous RNA produced by special selective splicing and participates in progression of diverse diseases. However, the role of circRNA in clear cell renal cell carcinoma (ccRCC) is still rarely reported. METHODS: We detected lower circ-AKT3 expression in ccRCC using the circular RNA microarray. Then, qPCR array was applied to verify the expression of circ-AKT3 in between 60 ccRCC tissues and adjacent normal tissues, as well as ccRCC cell lines and human normal kidney cell (HK-2). We investigated the function of circ-AKT3 in ccRCC in vitro and in vivo and detected underlying mechanisms by Western blotting, bioinformatic analysis, RNA pull-down assay and luciferase reporter assay. RESULTS: Circ-AKT3 was verified significantly downregulated in ccRCC. Knockdown of circ-AKT3 promoted ccRCC migration and invasion, while overexpression of circ-AKT3 suppressed ccRCC metastasis. Further, circ-AKT3/miR-296-3p/E-cadherin axis was shown responsible for circ-AKT3 inhibiting ccRCC metastasis. CONCLUSION: Circ-AKT3 suppresses ccRCC metastasis by enforcing E-cadherin expression through competitively binding miR-296-3p. Circ-AKT3 may therefore serve as a novel therapeutic to better suppress ccRCC metastasis.