scholarly journals Upregulation of Bag3 Exacerbates Cervical Cancer Progression by Impairing Immune Response and Inhibiting Cell Ferroptosis

2020 ◽  
Author(s):  
Yan Zhang ◽  
Jun Zhang ◽  
Yanping Jiang ◽  
Yuzi Zhao ◽  
Aili Tan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Response ◽  
Cell Proliferation ◽  
T Cells ◽  
Cancer Progression ◽  
Colony Formation ◽  
Migration And Invasion ◽  
Tnf Α ◽  
Ifn Γ ◽  
Invasion Capacity

Abstract Background: Cervical cancer remains a serious threat to women worldwide. Thus, effective strategies to treat cervical cancer are urgently needed. Bcl-2-associated athanogene 3 (Bag3) has been shown to be increased in several malignant neoplasms. However, little is known about the function of Bag3 in cervical cancer. We aimed to evaluate the function of Bag3 in cervical cancer progression.Method: qRT-PCR was carried out to test mRNA expression of Bag3, SLC7A11 and SLC3A2. Western blot analysis was conducted to detect protein expression of Bag3, SLC7A11 and SLC3A2. Cell proliferation was assessed using CCK-8, EdU and Colony formation assay. Flow cytometry assay was used to determine the frequency of IFN-γ- or TNF-α-producing CD8+ T cells. Transwell migration and invasion assay were carried out to detect cell migration and invasion capacity. Immunohistochemical staining was carried out to assess Bag3 and CD3 expressionResults: Bag3 was obviously elevated in cervical cancer tissues than in the adjacent normal tissues. Bag3 mRNA was upregulated in different cervical cancer cells (SiHa, C-33A, HT-3, and HeLa cells). SiHa cell proliferation, colony formation, and migration/invasion capacity were enhanced by Bag3 overexpression. Bag3 inhibited the immune response in cervical cancer. After C57BL6 mice were injected with Bag3-overexpressing SiHa cells, infiltrating CD3+ T cells around tumors were reduced. IFN-γ- and TNF-α-producing CD8+ T cells in tumor sections were remarkably inhibited by Bag3. Moreover, Ki-67+‑ and CD107a-producing CD8+ T cells were also suppressed. Bag3 repressed SiHa cell ferroptosis. Bag3 deletion inhibited cervical cancer development by improving the immune response and inducing ferroptosis. Conclusions: Taken together, these results indicated that Bag3 contributes to cervical cancer progression by impairing immune response and repressing cell ferroptosis.

scholarly journals The Role of Interleukin-10 (IL-10) in IL-15–Mediated T-Cell Responses

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4513-4521 ◽  
Author(s):  
Dieter Körholz ◽  
Ursula Banning ◽  
Halvard Bönig ◽  
Markus Grewe ◽  
Marion Schneider ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Interleukin 10 ◽  
T Cell Proliferation ◽  
Cell Production ◽  
Cd25 Expression ◽  
Tnf Α ◽  
Ifn Γ

Abstract Interleukin-15 (IL-15) is a potent T-cell stimulating factor, which has recently been used for pre-clinical in vivo immunotherapy. Here, the IL-15 effect on CD3-stimulated peripheral human T cells was investigated. IL-15 induced a significant T-cell proliferation and upregulated CD25 expression. IL-15 significantly enhanced T-cell production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-10. Between 10- and 100-fold greater concentrations of IL-15 were necessary to reach a biological effect equivalent to that of IL-2. Blockade of IL-2 binding to the high-affinity IL-2 receptor did not affect the IL-15 effects, suggesting that IL-15 did not act by inducing endogenous IL-2. Exogenously administered IL-10 significantly reduced the IL-15 and IL-2–mediated IFN-γ and TNF-α production, whereas T-cell proliferation and CD25 expression were not affected. The inhibitory effects of exogenously administered IL-10 on T-cell cytokine production appeared indirect, and are likely secondary to decreased IL-12 production by accessory cells. Inhibition of endogenous IL-10 binding to the IL-10 receptor significantly increased IFN-γ and TNF-α release from T cells. These data suggest that endogenous IL-10 can regulate activated T-cell production of IFN-γ and TNF-α via a paracrine negative feedback loop. The observations of this study could be of relevance for the therapeutic use of IL-15 in vivo.

scholarly journals LINC01128 expedites cervical cancer progression by regulating miR-383-5p/SFN axis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yi Hu ◽  
Yan Ma ◽  
Jie Liu ◽  
Yanlin Cai ◽  
Mengmeng Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
High Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Normal Tissues

Abstract Background Cervical cancer (CC), causing significant morbidity and mortality worldwide, is one of the most common gynecological malignancies in women. SFN has been reported as a potential prognostic marker with apparent high expression in tumors. Nevertheless, the function mechanism of SFN is not clear yet in CC. Methods The relative expressions of RNAs were detected by real-time quantitative PCR (RT-qPCR). Colony formation assay, EdU stained assay and CCK-8 assay were to check cell proliferation ability in CC. Flow cytometry and apoptosis related proteins analysis were used to measure cells apoptosis capacity. Luciferase reporter assay and RNA pull down assay were to verify the molecular mechanism. Results SFN was highly expressed in CC tissues and CC cell lines compared with normal tissues and normal cell line. After interfering SFN, cell proliferation, migration and invasion ability was inhibited as well as cell apoptosis ability was promoted. In subsequence, miR-383-5p exhibited conspicuous low expression in CC tissues. And miR-383-5p was found to bind to SFN and have anti-cancerous effects in CC. Moreover, LINC01128 displayed remarkable high expression in CC tissues. Besides, LINC01128 shortage could reduce the expression of SFN at mRNA and protein levels. And the affinity between LINC01128 and miR-383-5p was verified. In the end, it was proved that LINC01128 could enhance cell proliferation, migration and invasion as well as inhibit cell apoptosis by binding with miR-383-5p and upregulating SFN. Conclusion LINC01128 expedited cells cellular process in CC by binding with miR-383-5p to release SFN. Graphical Abstract

scholarly journals Why intracellular parasitism need not be a degrading experience for Mycobacterium

1997 ◽  
Vol 352 (1359) ◽  
pp. 1303-1310 ◽  
Author(s):  
David G. Russell ◽  
Sheila Sturgill-Koszycki ◽  
Tambryn Vanheyningen ◽  
Helen Collins ◽  
Ulrich E. Schaible
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Biochemical Analysis ◽  
Hydrolytic Activity ◽  
Intracellular Pathogens ◽  
Tnf Α ◽  
Mycobacterial Diseases ◽  
Ifn Γ ◽  
Cellular Immune ◽  
Endosomal System

The success of mycobacteria as pathogens hinges on their ability to infect and persist within the macrophages of their host. However, activation of host macrophages by cytokines from a productive cellular immune response can stimulate the cells to kill their resident pathogens. This suggests that the interaction between host cell and microbe is in delicate balance, which can be tipped in favour of either organism. Biochemical analysis of mycobacterial vacuoles has shown them to be integral to the host cell's recycling endosomal system. As such they show limited acidification and hydrolytic activity despite possession of known lysosomal constituents such as cathepsins D, B and L, and LAMP 1. Even in established infections, they remain dynamic compartments accessible to several plasmalemma–derived constituents. Once the macrophage has been activated by IFN–γ and TNF–α the vacuoles coalesce and acidify. This marks a distinct alteration in vacuole physiology and leads to stasis and death of the mycobacteria. Mycobacteria have developed several strategies to avoid this outcome. Most notably, live bacilli induce sustained release of IL–6 from infected macrophages. IL–6 blocks the ability of both polyclonal primary T cells and T–cell hybridomas to respond to appropriate stimuli. Such an activity could render the centers of infection foci, such as granulomas, anergic and thus avoid release of macrophage–activating cytokines. This paper discusses both the mechanisms by which mycobacteria try to ensure their success as intracellular pathogens and the relevance of these strategies to the overall understanding of mycobacterial diseases.

scholarly journals Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

2020 ◽  
Author(s):  
Nina Le Bert ◽  
Hannah E Clapham ◽  
Anthony T Tan ◽  
Wan Ni Chia ◽  
Christine YL Tham ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Inflammatory Cytokines ◽  
T Cell Activation ◽  
Cellular Immune Response ◽  
Cell Activation ◽  
Tnf Α ◽  
Specific Cellular Immune Response ◽  
Ifn Γ ◽  
Cellular Immune

AbstractThe efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-γ, IL-4, IL-6, IL-1β, TNF-α and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-γ and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance.

Anti-Leukemia Immune Responses in CML Patients Treated with Imatinib Mesylate.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1108-1108
Author(s):  
Christiane I.-U. Chen ◽  
Holden T. Maecker ◽  
Wesley H. Neal ◽  
Rhoda Falkow ◽  
Peter P. Lee
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Post Treatment ◽  
Leukemia Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Cytogenetic Remission ◽  
Pre Treatment

Abstract Imatinib mesylate, a selective inhibitor of the bcr/abl tyrosine kinase, has revolutionized the treatment of patients with chronic myelogenous leukemia (CML). Most CML patients in chronic phase achieve hematologic remission with imatinib, while some achieve cytogenetic remission. As imatinib is an oral agent with few side effects, it has rapidly become the first-line therapy for most CML patients. However, this therapy does not represent a cure, as patients who discontinue the drug invariably relapse. Furthermore, imatinib resistance is beginning to emerge in some patients. Hence, the need to find alternate, potentially curative, therapies for CML remains. To date, the only curative treatment for CML is allogeneic bone marrow or stem cell transplantation (ABMT). A major mechanism of the curative potential of ABMT is immunological, as evidenced by the poor clinical outcome with T cell-depleted ABMT, and the efficacy of donor lymphocyte infusions (DLI) upon relapse. We hypothesized that an effective anti-leukemia immune response may emerge in patients entering remission on imatinib which may contribute to its clinical effectiveness. If so, strategies to further enhance this anti-leukemia immune response may lead to a potential cure. To determine if CML patients in remission on imatinib develop anti-leukemia immune responses, blood and bone marrow samples from patients before and after treatment were collected and analyzed. Pre-treatment samples were utilized as sources of autologous leukemic cells to detect anti-leukemia immune responses in post-treatment samples in IFN-g ELISPOT assays. Pre-treatment samples alone, post-treatment samples alone, and when available, serial post-treatment samples mixed together served as controls. In 9 of 14 patients investigated, IFN-g release was detected in pre- and post-treatment samples together with a median response of 22 spots above background (range 10 – 56 dots, p<0.01), whereas serial post-treatment samples together in 8 patients yielded results similar to background (median 5, range 5 – 20). In 6 of these patients in hematologic (or cytogenetic) remission, sufficient cells were available to allow additional analyses via intracellular staining for IFN-g, TNF-a, and IL-2 in autologous leukemia stimulated T cells (CD4 and CD8) and NK cells. In 4 of 6 patients, leukemia-reactive T cells were detected, most prominently in CD4+ T cells expressing TNF-a (1.4 – 37%), followed by IL-2 (0.3 – 12%) and IFN-g (0.1 – 4.6%). NK cells did not show significant expression of these cytokines upon stimulation with autologous leukemia cells. In pre-treatment and post-treatment samples alone, IL-2, TNF-a, and IFN-g expression was not detectable (0 – 0.5%). These results suggest that a significant portion of CML patients in remission with imatinib develop an anti-leukemia immune response, most notably in CD4+ T cells. Mechanisms by which imatinib treatment leads to anti-leukemia immune responses, and the molecular targets to which these cells are directed, will be further investigated. This knowledge will be useful in the development of immunotherapy strategies against CML as well as other leukemias, and raises the hope that immunotherapy may be combined with imatinib to eradicate residual leukemia cells for a durable cure of the disease. intracellular cytokine staining CD4+ T Cells CD8+ T Cells IL-2 IFN- γ TNF- α IL-2 IFN- γ TNF- α pt 1 0.3 0 0.8 0.1 0.1 0.5 pt 1 0.3 0.1 1.4 0.1 0.1 0.4 pt 2 2.6 0.8 10.3 2.2 2.1 6.1 pt 3 21 2 37 2.3 0.7 1.7 pt 4 12 4.6 19 6.3 1.8 5.8

scholarly journals Ineffective Cellular Immune Response Associated with T-Cell Apoptosis in Susceptible Mycobacterium bovisBCG-Infected Mice

2000 ◽  
Vol 68 (7) ◽  
pp. 4264-4273 ◽  
Author(s):  
Laurent Kremer ◽  
Jérôme Estaquier ◽  
Isabelle Wolowczuk ◽  
Franck Biet ◽  
Jean-Claude Ameisen ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Cell Apoptosis ◽  
T Cell Proliferation ◽  
T Cell Apoptosis ◽  
Tnf Α

ABSTRACT It has previously been reported that inhibition of delayed-type hypersensitivity-mediating functions of T cells during mycobacterial infection in mice is haplotype dependent. In the present study, we show that Mycobacterium bovis BCG infection induced, in susceptible C57BL/6 and BALB/c mice but not in resistant C3H/HeJ and DBA/2 mice, an important splenomegaly. An in vitro defect in T-cell proliferation in response to T-cell receptor (TCR) stimulation with mitogens or anti-CD3 antibodies was associated with enhanced levels of CD4+ and CD8+ T-cell apoptosis in susceptible but not in resistant mice 2 weeks after infection. Further investigations of C57BL/6 and C3H/HeJ mice revealed that in vivo splenomegaly was associated with destruction of the lymphoid tissue architecture, liver cellular infiltrates, and increased numbers of apoptotic cells in both spleen and liver tissue sections. Infection of C57BL/6 mice but not of C3H/HeJ mice induced massive production of tumor necrosis factor alpha (TNF-α) in serum, as well as an increase in Fas and Fas ligand (FasL) expression in T cells. In vitro addition of neutralizing anti-TNF-α antibodies led to a significant reduction in CD3-induced T-cell apoptosis of both CD4+ and CD8+ T cells of C57BL/6 mice, while the blockade of Fas-FasL interactions reduced apoptosis only in CD4+ but not in CD8+ T cells. Together, these results suggest that TNF-α and Fas-FasL interactions play a role in the activation-induced cell death (AICD) process associated with a defect in T-cell proliferation of the susceptible C57BL/6 mice. T-cell death by apoptosis may represent one of the important components of the ineffective immune response against mycobacterium-induced immunopathology in susceptible hosts.

scholarly journals IDO and CD40 May Be Key Molecules for Immunomodulatory Capacity of the Primed Tonsil-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5772
Author(s):  
Hyun-Joo Lee ◽  
Harry Jung ◽  
Dong-Kyu Kim
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Cd4 T Cells ◽  
Immune Cell ◽  
Suppressive Effect ◽  
Tnf Α ◽  
Immunomodulatory Capacity ◽  
Ifn Γ

Background: Tonsil-derived mesenchymal stem cells (T-MSCs) were reported to have suppressive effect on T cells, yet much remains unknown about the underlying mechanisms supporting this effect. We investigated the underlying mechanism of the immunomodulatory effect of T-MSCs on immune cell proliferation and cytokine production. Methods: We isolated T-MSCs from human palatine tonsil and evaluated the immunomodulatory capacity using RT-PCR, ELISA, and flow cytometry. Additionally, we assessed the expression of various soluble factors and several costimulatory molecules to detect the priming effect on T-MSCs. Results: T-MSCs significantly inhibited the immune cell proliferation and cytokine expression (TNF-α and IFN-γ) in the direct co-culture, but there was no suppressive effect in indirect co-culture. Additionally, we detected a remarkably higher expression of indoleamine 2,3-dioxygenase (IDO) in the primed T-MSCs having co-expression CD40. Moreover, immune cells or CD4+ T cells showed lower TNF-α, IFN-γ, and IL-4 expression when the primed T-MSC were added; whereas those findings were reversed when the inhibitor for IDO (not IL-4) or CD40 were added. Furthermore, T-bet and GATA3 levels were significantly decreased in the co-cultures of the primed T-MSCs and CD4+ T cells; whereas those findings were reversed when we added the neutralizing anti-CD40 antibody. Conclusions: Primed T-MSCs expressing IDO and CD40 may have immunomodulatory capacity via Th1-mediated and Th2-mediated immune response.

scholarly journals Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Lili Mi ◽  
Lianhui Lei ◽  
Xiaolei Yin ◽  
Ning Li ◽  
Jianfei Shi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Colony Formation ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
The Impact

Abstract Background: Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. Methods: The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. Results: Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. Conclusion: Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment.

scholarly journals Low-Dose Decitabine Augments the Activation and Anti-Tumor Immune Response of IFN-γ+ CD4+ T Cells Through Enhancing IκBα Degradation and NF-κB Activation

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiang Li ◽  
Liang Dong ◽  
Jiejie Liu ◽  
Chunmeng Wang ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Low Dose ◽  
T Cell Proliferation ◽  
Ifn Γ ◽  
Iκbα Degradation

BackgroundCD4+ T cells play multiple roles in controlling tumor growth and increasing IFN-γ+ T-helper 1 cell population could promote cell-mediated anti-tumor immune response. We have previously showed that low-dose DNA demethylating agent decitabine therapy promotes CD3+ T-cell proliferation and cytotoxicity; however, direct regulation of purified CD4+ T cells and the underlying mechanisms remain unclear.MethodsThe effects of low-dose decitabine on sorted CD4+ T cells were detected both in vitro and in vivo. The activation, proliferation, intracellular cytokine production and cytolysis activity of CD4+ T cells were analyzed by FACS and DELFIA time-resolved fluorescence assays. In vivo ubiquitination assay was performed to assess protein degradation. Moreover, phosphor-p65 and IκBα levels were detected in sorted CD4+ T cells from solid tumor patients with decitabine-based therapy.ResultsLow-dose decitabine treatment promoted the proliferation and activation of sorted CD4+ T cells, with increased frequency of IFN-γ+ Th1 subset and enhanced cytolytic activity in vitro and in vivo. NF-κB inhibitor, BAY 11-7082, suppressed decitabine-induced CD4+ T cell proliferation and IFN-γ production. In terms of mechanism, low-dose decitabine augmented the expression of E3 ligase β-TrCP, promoted the ubiquitination and degradation of IκBα and resulted in NF-κB activation. Notably, we observed that in vitro low-dose decitabine treatment induced NF-κB activation in CD4+ T cells from patients with a response to decitabine-primed chemotherapy rather than those without a response.ConclusionThese data suggest that low-dose decitabine potentiates CD4+ T cell anti-tumor immunity through enhancing IκBα degradation and therefore NF-κB activation and IFN-γ production.

scholarly journals Circ-CCDC66 Upregulates REXO1 Expression to Aggravate Cervical Cancer Progression Via Restraining miR-452-5p

2020 ◽  
Author(s):  
Yun Zhang ◽  
Xing Li ◽  
Jun Zhang ◽  
Lin Mao
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Tumor Model ◽  
Tumor Stage ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Fractionation ◽  
Real Time Quantitative Pcr ◽  
Cancer Tumor

Abstract BackgroundCervical cancer is one most common cancer types among females around the world. CircRNAs have been revealed to participate in multiple biological functions, and are involved in many diseases’ progression. In current study, we aimed to elucidate whether circ-CCDC66 participates cervical cancer progression. MethodsReal-time quantitative PCR (RT-qPCR) was conducted to measure the expression of circ-CCDC66, miR-452-5p, and REXO1 mRNA. Cell fractionation assay and RNA fluorescence in situ hybridization (FISH) were performed to locate circ-CCDC66 in cells. Cell proliferation ability was detected using cell account kit 8 (CCK-8). TRANSWELL assay was applied to evaluate cell migration or invasion ability. Bioinformatics analysis, biotinylated RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assays were conducted to assess the association between miR-452 and circ-CCDC66 or REXO1. Western blot was applied to measure the protein expression of REXO1. Animal tumor model was used to assess the effect of circ-CCDC66 in vivo.ResultsCirc-CCDC66 was upregulated in cervical cancer tumor tissues, and correlated with tumor stage and tumor size. Downregulation of circ-CCDC66 inhibited cervical cancer cell proliferation, migration, and invasion. Circ-CCDC66 was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. MiR-452 directly targeted REXO1. The effects of circ-CCDC66 on cervical cancer cells were functioned through miR-452-5p/REXO1 axis. In animal experiment, downregulation of circ-CCDC66 was found to suppress tumor growth in vivo.ConclusionOur results demonstrated the effects of circ-CCDC66/miR-452-5p/REXO1 axis in cervical cancer progression, we might provide a novel therapeutic target for cervical cancer.

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