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1.
Int J Cancer ; 150(2): 279-289, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34528705

RESUMO

Germline variants might predict cancer progression. Bevacizumab improves overall survival (OS) in patients with advanced cancers. No biomarkers are available to identify patients that benefit from bevacizumab. A meta-analysis of genome-wide association studies (GWAS) was conducted in 1,520 patients from Phase III trials (CALGB 80303, 40503, 80405 and ICON7), where bevacizumab was randomized to treatment without bevacizumab. We aimed to identify genes and single nucleotide polymorphisms (SNPs) associated with survival independently of bevacizumab treatment or through interaction with bevacizumab. A cause-specific Cox model was used to test the SNP-OS association in both arms combined (prognostic), and the effect of SNPs-bevacizumab interaction on OS (predictive) in each study. The SNP effects across studies were combined using inverse variance. Findings were tested for replication in advanced colorectal and ovarian cancer patients from The Cancer Genome Atlas (TGCA). In the GWAS meta-analysis, patients with rs680949 in PRUNE2 experienced shorter OS compared to patients without it (P = 1.02 × 10-7 , hazard ratio [HR] = 1.57, 95% confidence interval [CI] 1.33-1.86), as well as in TCGA (P = .0219, HR = 1.58, 95% CI 1.07-2.35). In the GWAS meta-analysis, patients with rs16852804 in BARD1 experienced shorter OS compared to patients without it (P = 1.40 × 10-5 , HR = 1.51, 95% CI 1.25-1.82) as well as in TCGA (P = 1.39 × 10-4 , HR = 3.09, 95% CI 1.73-5.51). Patients with rs3795897 in AGAP1 experienced shorter OS in the bevacizumab arm compared to the nonbevacizumab arm (P = 1.43 × 10-5 ). The largest GWAS meta-analysis of bevacizumab treated patients identified PRUNE2 and BARD1 (tumor suppressor genes) as prognostic genes of colorectal and ovarian cancer, respectively, and AGAP1 as a potentially predictive gene that interacts with bevacizumab with respect to patient survival.

4.
World J Gastroenterol ; 27(39): 6701-6714, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34754162

RESUMO

BACKGROUND: Standard liver weight (SLW) is frequently used in deceased donor liver transplantation to avoid size mismatches with the recipient. However, some deceased donors (DDs) have fatty liver (FL). A few studies have reported that FL could impact liver size. To the best of our knowledge, there are no relevant SLW models for predicting liver size. AIM: To demonstrate the relationship between FL and total liver weight (TLW) in detail and present a related SLW formula. METHODS: We prospectively enrolled 212 adult DDs from West China Hospital of Sichuan University from June 2019 to February 2021, recorded their basic information, such as sex, age, body height (BH) and body weight (BW), and performed abdominal ultrasound (US) and pathological biopsy (PB). The chi-square test and kappa consistency score were used to assess the consistency in terms of FL diagnosed by US relative to PB. Simple linear regression analysis was used to explore the variables related to TLW. Multiple linear regression analysis was used to formulate SLW models, and the root mean standard error and interclass correlation coefficient were used to test the fitting efficiency and accuracy of the model, respectively. Furthermore, the optimal formula was compared with previous formulas. RESULTS: Approximately 28.8% of DDs had FL. US had a high diagnostic ability (sensitivity and specificity were 86.2% and 92.9%, respectively; kappa value was 0.70, P < 0.001) for livers with more than a 5% fatty change. Simple linear regression analysis showed that sex (R2, 0.226; P < 0.001), BH (R2, 0.241; P < 0.001), BW (R2, 0.441; P < 0.001), BMI (R2, 0.224; P < 0.001), BSA (R2, 0.454; P < 0.001) and FL (R2, 0.130; P < 0.001) significantly impacted TLW. In addition, multiple linear regression analysis showed that there was no significant difference in liver weight between the DDs with no steatosis and those with steatosis within 5%. Furthermore, in the context of hepatic steatosis, TLW increased positively (non-linear); compared with the TLW of the non-FL group, the TLW of the groups with hepatic steatosis within 5%, between 5% and 20% and more than 20% increased by 0 g, 90 g, and 340 g, respectively. A novel formula, namely, -348.6 + (110.7 x Sex [0 = Female, 1 = Male]) + 958.0 x BSA + (179.8 x FLUS [0 = No, 1 = Yes]), where FL was diagnosed by US, was more convenient and accurate than any other formula for predicting SLW. CONCLUSION: FL is positively correlated with TLW. The novel formula deduced using sex, BSA and FLUS is the optimal formula for predicting SLW in adult DDs.


Assuntos
Fígado Gorduroso , Transplante de Fígado , Adulto , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Fígado/diagnóstico por imagem , Doadores Vivos , Masculino , Tamanho do Órgão , Estudos Prospectivos
5.
Oncogene ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785777

RESUMO

Nerve infiltration in the tumor microenvironment is emerging as a promoter of cancer progression that could be targeted in therapies, but the mechanisms initiating tumor innervation remain to be elucidated. Here we report that endoplasmic reticulum (ER) stress in cancer cells is transmitted to neuronal cells, resulting in neurite outgrowth and tumor innervation. In vitro, the induction of ER stress in various human cancer cells resulted in the synthesis and release of the precursor for brain-derived neurotrophic factor (proBDNF) through a mechanism dependent on the transcription factor X-box binding protein 1 (XBP1). Cancer cell-released proBDNF was found to mediate the transmission of ER stress to neurons, resulting in the stimulation of neurite outgrowth. Next-generation sequencing indicated the increased expression of the Egl-9 family hypoxia inducible factor 3 (EGLN3) that was mediated by c-MYC and necessary to neurite outgrowth induced by proBDNF. In orthotopic tumor xenograft, ER stress stimulated XBP1 and proBDNF expression as well as tumor innervation. Anti-proBDNF antibody inhibited both tumor innervation and cancer progression induced by ER stress. Interestingly, the chemotherapeutic drug 5-Fluorouracil (5-FU) was found to induce ER stress and tumor innervation, and this effect was inhibited by anti-proBDNF antibody. Finally, in human tumors, cancer tissues with nerve infiltration expressed high XBP1 and proBDNF while EGLN3 was upregulated in infiltrated nerves. This study reveals that ER stress participates in tumor innervation through the release of proBDNF and that targeting this pathway could be used in future therapies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34824007

RESUMO

Hydrazine plays an important role in chemistry, pharmaceuticals, agriculture and aerospace. However, it is not to be underestimated and has been identified as harmful to the human body. Therefore, it is significant and urgent to develop the detection of hydrazine in vivo and in vitro. Here, the probe TAN was synthesized by using benzothiazole derivatives as the fluorophore and 2,3-diaminomaleonitrile as the identified group to detect hydrazine. The presence of hydrazine resulted in a colorimetric and ratiometric fluorescence response of the probe based on the formation of hydrazone. The detection limit of TAN was 0.31 µM for hydrazine. In addition, the probe TAN was successfully used to visualize hydrazine in living HepG-2 cells and mouse with low cytotoxicity and excellent biocompatibility.

7.
Int J Mol Sci ; 22(22)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34830457

RESUMO

Heterodera schachtii is a well-known cyst nematode that causes serious economic losses in sugar beet production every year. Rapid and visual detection of H. schachtii is essential for more effective prevention and control. In this study, a species-specific recombinase polymerase amplification (RPA) primer was designed from a specific H. schachtii sequence-characterized amplified region (SCAR) marker. A band was obtained in reactions with DNA from H. schachtii, but absent from nontarget cyst nematodes. The RPA results could be observed by the naked eye, using a lateral flow dipstick (LFD). Moreover, we combined CRISPR technology with RPA to identify positive samples by fluorescence detection. Sensitivity analysis indicated that 10-4 single cysts and single females, 4-3 single second-stage juveniles, and a 0.001 ng genomic DNA template could be detected. The sensitivity of the RPA method for H. schachtii detection is not only higher than that of PCR and qPCR, but can also provide results in <1 h. Consequently, the RPA assay is a practical and useful diagnostic tool for early diagnosis of plant tissues infested by H. schachtii. Sugar beet nematodes were successfully detected in seven of 15 field sugar beet root samples using the RPA assay. These results were consistent with those achieved by conventional PCR, indicating 100% accuracy of the RPA assay in field samples. The RPA assay developed in the present study has the potential for use in the direct detection of H. schachtii infestation in the field.

8.
Nat Commun ; 12(1): 6260, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716306

RESUMO

Cochlear implants restore hearing in patients with severe to profound deafness by delivering electrical stimuli inside the cochlea. Understanding stimulus current spread, and how it correlates to patient-dependent factors, is hampered by the poor accessibility of the inner ear and by the lack of clinically-relevant in vitro, in vivo or in silico models. Here, we present 3D printing-neural network co-modelling for interpreting electric field imaging profiles of cochlear implant patients. With tuneable electro-anatomy, the 3D printed cochleae can replicate clinical scenarios of electric field imaging profiles at the off-stimuli positions. The co-modelling framework demonstrated autonomous and robust predictions of patient profiles or cochlear geometry, unfolded the electro-anatomical factors causing current spread, assisted on-demand printing for implant testing, and inferred patients' in vivo cochlear tissue resistivity (estimated mean = 6.6 kΩcm). We anticipate our framework will facilitate physical modelling and digital twin innovations for neuromodulation implants.

9.
Br J Cancer ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34616010

RESUMO

BACKGROUND: Hypertension and proteinuria are common bevacizumab-induced toxicities. No validated biomarkers are available for identifying patients at risk of these toxicities. METHODS: A genome-wide association study (GWAS) meta-analysis was performed in 1039 bevacizumab-treated patients of European ancestry in four clinical trials (CALGB 40502, 40503, 80303, 90401). Grade ≥2 hypertension and proteinuria were recorded (CTCAE v.3.0). Single-nucleotide polymorphism (SNP)-toxicity associations were determined using a cause-specific Cox model adjusting for age and sex. RESULTS: The most significant SNP associated with hypertension with concordant effect in three out of the four studies (p-value <0.05 for each study) was rs6770663 (A > G) in KCNAB1, with the G allele increasing the risk of hypertension (p-value = 4.16 × 10-6). The effect of the G allele was replicated in ECOG-ACRIN E5103 in 582 patients (p-value = 0.005). The meta-analysis of all five studies for rs6770663 led to p-value = 7.73 × 10-8, close to genome-wide significance. The most significant SNP associated with proteinuria was rs339947 (C > A, between DNAH5 and TRIO), with the A allele increasing the risk of proteinuria (p-value = 1.58 × 10-7). CONCLUSIONS: The results from the largest study of bevacizumab toxicity provide new markers of drug safety for further evaluations. SNP in KCNAB1 validated in an independent dataset provides evidence toward its clinical applicability to predict bevacizumab-induced hypertension. ClinicalTrials.gov Identifier: NCT00785291 (CALGB 40502); NCT00601900 (CALGB 40503); NCT00088894 (CALGB 80303) and NCT00110214 (CALGB 90401).

10.
Front Plant Sci ; 12: 746972, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659317

RESUMO

There are numerous non-volatile metabolites in the fresh shoots of tea plants. However, we know little about the complex relationship between the content of these metabolites and their gene expression levels. In investigating this, this study involved non-volatile metabolites from 68 accessions of tea plants that were detected and identified using untargeted metabolomics. The tea accessions were divided into three groups from the results of a principal component analysis based on the relative content of the metabolites. There were differences in variability between the primary and secondary metabolites. Furthermore, correlations among genes, gene metabolites, and metabolites were conducted based on Pearson's correlation coefficient (PCC) values. This study offered several significant insights into the co-current network of genes and metabolites in the global genetic background. Thus, the study is useful for providing insights into the regulatory relationship of the genetic basis for predominant metabolites in fresh tea shoots.

12.
ACS Appl Mater Interfaces ; 13(36): 42396-42410, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472332

RESUMO

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.

13.
Acta Pharm Sin B ; 11(8): 2306-2325, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34522589

RESUMO

Blood-brain barrier (BBB) strictly controls matter exchange between blood and brain, and severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy of brain diseases. However, during the onset and progression of brain diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer's disease, Parkinson's disease, epilepsy, stroke, traumatic brain injury and brain tumor. The advances on optimization of small molecules for BBB crossing and non-systemic administration routes (e.g., intranasal treatment) for BBB bypassing are not included in this review.

14.
Cell Rep ; 37(1): 109793, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34587478

RESUMO

The mortality risk of coronavirus disease 2019 (COVID-19) patients has been linked to the cytokine storm caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the inflammatory responses shared between COVID-19 and other infectious diseases that feature cytokine storms may therefore help in developing improved therapeutic strategies. Here, we use integrative analysis of single-cell transcriptomes to characterize the inflammatory signatures of peripheral blood mononuclear cells from patients with COVID-19, sepsis, and HIV infection. We identify ten hyperinflammatory cell subtypes in which monocytes are the main contributors to the transcriptional differences in these infections. Monocytes from COVID-19 patients share hyperinflammatory signatures with HIV infection and immunosuppressive signatures with sepsis. Finally, we construct a "three-stage" model of heterogeneity among COVID-19 patients, related to the hyperinflammatory and immunosuppressive signatures in monocytes. Our study thus reveals cellular and molecular insights about inflammatory responses to SARS-CoV-2 infection and provides therapeutic guidance to improve treatments for subsets of COVID-19 patients.


Assuntos
COVID-19/sangue , COVID-19/imunologia , Infecções por HIV/sangue , Leucócitos Mononucleares/metabolismo , SARS-CoV-2/imunologia , Sepse/sangue , Transcriptoma , COVID-19/virologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/imunologia , Citocinas/sangue , Análise de Dados , Conjuntos de Dados como Assunto , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Imunossupressão , Inflamação/sangue , Leucócitos Mononucleares/imunologia , Sepse/imunologia , Análise de Célula Única
15.
Sci Rep ; 11(1): 18263, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521930

RESUMO

Shikonin is the main component of the traditional Chinese medicine comfrey, which can inhibit the activity of PKM2 by regulating glycolysis and ATP production. Rheumatoid arthritis synovial cells (RA-FLSs) have been reported to increase glycolytic activity and have other similar hallmarks of metabolic activity. In this study, we investigated the effects of shikonin on glycolysis, mitochondrial function, and cell death in RA-FLSs. The results showed that shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway. Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-α, IL-6, IL-8, IL-10, IL-17A, and IL-1ß while showing less toxicity to the liver and kidney.

16.
ACS Nano ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34382768

RESUMO

Metabolic interactions between different cell types in the tumor microenvironment (TME) often result in reprogramming of the metabolism to be totally different from their normal physiological processes in order to support tumor growth. Many studies have attempted to inhibit tumor growth and activate tumor immunity by regulating the metabolism of tumors and other cells in TME. However, metabolic inhibitors often suffer from the heterogeneity of tumors, since the favorable metabolic regulation of malignant cells and other cells in TME is often inconsistent with each other. Therefore, we reported the design of a pH-sensitive drug delivery system that targets different cells in TME successively. Outer membrane vesicles (OMVs) derived from Gram-negative bacteria were applied to coload paclitaxel (PTX) and regulated in development and DNA damage response 1 (Redd1)-siRNA and regulate tumor metabolism microenvironment and suppress tumor growth. Our siRNA@M-/PTX-CA-OMVs could first release PTX triggered by the tumor pH (pH 6.8). Then the rest of it would be taken in by M2 macrophages to increase their level of glycolysis. Great potential was observed in TAM repolarization, tumor suppression, tumor immune activation, and TME remolding in the triple-negative breast cancer model. The application of the OMV provided an insight for establishing a codelivery platform for chemical drugs and genetic medicines.

17.
Int J Mol Med ; 48(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34368868

RESUMO

Following the publication of this paper, an interested reader drew to the attention of the authors and the Editorial Office that a number of the data panels shown for the cell migration assays in Figs. 1, 3, 4 and 5 contained overlapping data, such that the indicated results purportedly representing different experiments were derived from the same original sources. Furthermore, it was noted that the same scratch­wound assay data had apparently been included in four of the panels shown in Fig. 5D that were intended to represent different experiments performed under different conditions. After having investigated the matter internally, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors did not offer a satisfactory response to account for the various issues identified in these figures. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 31: 1234­1242, 2013; DOI: 10.3892/ijmm.2013.1292].

18.
Cell Prolif ; 54(10): e13114, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34435402

RESUMO

OBJECTIVES: Bone marrow-derived cells (BMDCs), especially mesenchymal stem cells (MSCs), may be involved in the development of Helicobacter pylori-associated gastric cancer (GC) in mice, but the specific mechanism remains unclear, and evidence from human studies is lacking. MATERIALS AND METHODS: To verify the role of BM-MSCs in H pylori-associated GC, green fluorescent protein (GFP)-labelled BM-MSCs were transplanted into the subserosal layers of the stomach in a mouse model of chronic H pylori infection. Three months post-transplantation, the mice were sacrificed, and the gastric tissues were subjected to histopathological and immunofluorescence analyses. In addition, we performed fluorescence in situ hybridization (FISH) and immunofluorescence analyses of gastric tissue from a female patient with H pylori infection and a history of acute myeloid leukaemia who received a BM transplant from a male donor. RESULTS: In mice with chronic H pylori infection, GFP-labelled BM-MSCs migrated from the serous layer to the mucosal layer and promoted GC progression. The BM-MSCs differentiated into pan-cytokeratin-positive epithelial cells and α-smooth muscle actin-positive cancer-associated fibroblasts (CAFs) by secreting the protein thrombospondin-2. FISH analysis of gastric tissue from the female patient revealed Y-chromosome-positive cells. Immunofluorescence analyses further confirmed that Y-chromosome-positive cells showed positive BM-MSCs marker. These results suggested that allogeneic BMDCs, including BM-MSCs, can migrate to the stomach under chronic H pylori infection. CONCLUSIONS: Taken together, these findings imply that BM-MSCs participate in the development of chronic H pylori-associated GC by differentiating into both gastric epithelial cells and CAFs.


Assuntos
Células da Medula Óssea/metabolismo , Medula Óssea/metabolismo , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neoplasias Gástricas/metabolismo , Trombospondinas/metabolismo , Animais , Medula Óssea/microbiologia , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Feminino , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Gástricas/microbiologia
19.
Pacing Clin Electrophysiol ; 44(11): 1824-1831, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34427332

RESUMO

OBJECTIVE: To investigate theoptimal idarucizumab (dabigatran antagonist) usage strategy for patients with acute pericardial tamponade receiving uninterrupted dabigatran during catheter ablation for atrial fibrillation (AF). METHODS: Ten patients presenting acute pericardial tamponade while receiving uninterrupted dabigatran during catheter ablation for AF in Beijing Anzhen Hospital from January 2019 to July 2020 were enrolled and retrospectively analyzed. A "wait and see" strategy of idarucizumab was carried out for all patients; in brief, idarucizumab was applied following pericardiocentesis, comprehensive evaluation of bleeding and hemostasis. RESULTS: There were five males, five paroxysmal AF, and the average age of the patients was 64.0 ± 9.8 years. Among the 10 patients, four were treated with dabigatran 110 mg, six were treated with dabigatran 150 mg, and one was simultaneously given clopidogrel. The average time from pericardial tamponade to the last dose of dabigatran was 8.2 ± 3.4 h. All patients underwent pericardiocentesis successfully, and the average drainage volume was 322.5 ml (220.0 ± 935.0 ml). For reversal anticoagulation, six patients received protamine, and five patients received idarucizumab. Of the five patients who were treated with idarucizumab, four presented exact hemostasis, except for one patient who underwent continuous drainage and finally received surgery repair. The average time to restart anticoagulation was 1.1 ± 0.3 days after the procedure, and no rebleeding, embolism or deaths were observed. CONCLUSION: The "wait and see" strategy of idarucizumab for acute pericardial tamponade during the perioperative period of catheter ablation for AF may be safe and feasible.

20.
Drug Dev Res ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34368980

RESUMO

Circular RNA (circRNA) have been found to play an important role in the progression of many diseases, including interstitial cystitis (IC). However, the role of circTHBS1 in IC progression is still unclear. Exploring the role and potential molecular mechanism of circTHBS1 in the development of IC. The enzyme-linked immunosorbent assay was used to assess the levels of inflammatory cytokines. The expression levels of circTHBS1, microRNA (miR)-139-5p, and mitofusin 2 (MFN2) were evaluated using quantitative real-time PCR. Cell proliferation and migration were determined using MTT assay, Edu staining, and transwell assay. The protein levels of epithelial-mesenchymal transition (EMT) markers and MFN2 were examined using western blot analysis. The relationship between miR-139-5p and circTHBS1 or MFN2 was confirmed using the dual-luciferase reporter assay and RIP assay. CircTHBS1 was highly repressed in IC tissues and cells, and its expression was positively correlated with the inflammatory response of IC patients. CircTHBS1 could promote the proliferation, migration, EMT process, and inflammation of IC cells, while its knockdown had an opposite effect. CircTHBS1 could serve as a sponge of miR-139-5p, and miR-139-5p could participate in the regulation of circTHBS1 on IC cell progression. In addition, miR-139-5p could target MFN2, and it could inhibit the progression of IC cells by targeting MFN2. Furthermore, circTHBS1 sponged miR-139-5p to positively regulate MFN2. CircTHBS1 promoted IC cell proliferation, migration, EMT process, and inflammation by regulating the miR-139-5p/MFN2 axis indicating that circTHBS1 might be a potential target for IC treatment.

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