scholarly journals circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Botai Li ◽  
Lili Zhu ◽  
Chunlai Lu ◽  
Cun Wang ◽  
Hui Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Immunity ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Circular Rnas ◽  
Small Cell Lung ◽  
Protein Ubiquitination ◽  
Cellular Immune

AbstractCircular RNAs (circRNA) are a class of covalently closed single-stranded RNAs that have been implicated in cancer progression. Here we identify circNDUFB2 to be downregulated in non-small cell lung cancer (NSCLC) tissues, and to negatively correlate with NSCLC malignant features. Elevated circNDUFB2 inhibits growth and metastasis of NSCLC cells. Mechanistically, circNDUFB2 functions as a scaffold to enhance the interaction between TRIM25 and IGF2BPs, a positive regulator of tumor progression and metastasis. This TRIM25/circNDUFB2/IGF2BPs ternary complex facilitates ubiquitination and degradation of IGF2BPs, with this effect enhanced by N6-methyladenosine (m6A) modification of circNDUFB2. Moreover, circNDUFB2 is also recognized by RIG-I to activate RIG-I-MAVS signaling cascades and recruit immune cells into the tumor microenvironment (TME). Our data thus provide evidences that circNDUFB2 participates in the degradation of IGF2BPs and activation of anti-tumor immunity during NSCLC progression via the modulation of both protein ubiquitination and degradation, as well as cellular immune responses.

scholarly journals CALR-TLR4 Complex Inhibits Non-Small Cell Lung Cancer Progression by Regulating the Migration and Maturation of Dendritic Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruo Chen ◽  
Min Huang ◽  
Xu Yang ◽  
Xiao-Hong Chen ◽  
Ming-Yan Shi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Small Cell Lung Cancer ◽  
Tumor Immunity ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Myd88 Signaling

BackgroundLung cancer is a common malignant tumor that threatens human life and is associated with high morbidity and mortality rates. Calreticulin (CALR) is a antigen characteristic of immunogenic cell death in non-small cell lung cancer (NSCLC), which is closely related to anti-tumor immunity, but its specific mechanism in anti-tumor immunity remains unclear.MethodsImmunohistochemical staining was performed to detect the expression of CALR and dendritic cell-lysosome-associated membrane glycoprotein (DC-LAMP) in NSCLC tissues. The cell supernatant was used to induce migration and maturation of dendritic cells (DCs). Western blot and real-time PCR were used to investigate the corresponding molecule expression in the CALR-Toll-like receptor 4 (TLR4)-MyD88 signaling pathway. In vivo experiments were conducted to evaluate the role of mCALR in lung cancer progression.ResultsThe expression of CALR on NSCLC cell membrane (mCALR) and DC infiltration in NSCLC were positively correlated and were closely related to the prognosis of NSCLC patients. Moreover, mCALR facilitated the migration and maturation of DCs by activating CALR-TLR4-MyD88 signaling and increasing the secretion of TNFα and CCL19, which was inhibited by the loss of TLR4. In vivo experiments demonstrated that mCALR inhibited lung cancer progression by facilitating DC infiltration in lung cancer tissues.ConclusionOur study explores the function and mechanism of the CALR-TLR4 complex in DC migration and maturation and investigates the inhibitory effect of the CALR-TLR4 complex on lung cancer progression, providing a theoretical basis and ideas for immunotherapy of NSCLC.

scholarly journals circ_0002346 Suppresses Non-Small-Cell Lung Cancer Progression Depending on the Regulation of the miR-582-3p/STXBP6 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Weijie Wang ◽  
Yi Lin ◽  
Guanghui Zhang ◽  
Guofu Shi ◽  
Yongsheng Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Small Cell Lung ◽  
Antitumor Effects

Background. Accumulating articles have reported the pivotal regulatory roles of circular RNAs (circRNAs) in non-small-cell lung cancer (NSCLC) tumorigenesis. Here, our purpose was to explore the role of circ_0002346 in NSCLC progression and its associated mechanism. Methods. Cell proliferation ability was assessed by a 5-ethynyl-2 ′ -deoxyuridine (EDU) assay and a colony formation assay. Transwell assays were conducted to analyze cell migration and invasion abilities. Cell apoptosis was analyzed by flow cytometry and by using a caspase3 activity assay kit. The glycolysis of NSCLC cells was analyzed using a fluorescence-based glucose/lactate assay kit. A dual-luciferase reporter assay and an RNA pull-down assay were performed to verify the binding relationship between microRNA-582-3p (miR-582-3p) and circ_0002346 or syntaxin-binding protein 6 (STXBP6). Results. circ_0002346 level was prominently downregulated in NSCLC tissues and cell lines. circ_0002346 overexpression significantly suppressed the proliferation, migration, invasion, and glycolysis and triggered the apoptosis of NSCLC cells. circ_0002346 directly interacted with miR-582-3p, and circ_0002346 overexpression-mediated antitumor effects in NSCLC cells were partly reversed by miR-582-3p overexpression. miR-582-3p directly interacted with the 3 ′ untranslated region (3 ′ UTR) of STXBP6, and STXBP6 silencing partly counteracted circ_0002346 overexpression-mediated antitumor influences in NSCLC cells. circ_0002346 can upregulate the expression of STXBP6 by acting as a miR-582-3p sponge in NSCLC cells. circ_0002346 overexpression suppressed xenograft tumor growth in vivo. Conclusion. circ_0002346 overexpression suppressed the malignant properties of NSCLC cells by binding to miR-582-3p to induce the expression of STXBP6.

Circular RNA SMARCA5 suppressed non-small cell lung cancer progression by regulating miR-670-5p/RBM24 axis

2020 ◽  
Vol 52 (10) ◽  
pp. 1071-1080
Author(s):  
Danjie Zhang ◽  
Yuefeng Ma ◽  
Zhenchuan Ma ◽  
Shiyuan Liu ◽  
Liangzhang Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Rna Binding ◽  
Circular Rna ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Small Cell Lung

Abstract Circular RNAs (circRNAs) have good stability and long half-life in blood and other body fluid, and possess regulatory effects on various biological processes as miRNA/RNA-binding protein sponges, or by competing endogenous RNA, indicating their great potential as biomarkers or targets of cancer therapy. In this study, we mainly explored the role and mechanism of circular RNA SMARCA5 (circsSMARCA5) in non-small cell lung cancer (NSCLC). Quantitative RT-PCR was applied to measure the expression levels of genes, and then, the relationships among circsSMARCA5, microRNA-670-5p (miR-670-5p), and RBM24 were further analyzed. Animal and cell experiments were performed to explore the functions of circsSMARCA5 in NSCLC cells. The results showed that circsSMARCA5 was expressed at low level in NSCLC tissues and cells, while miR-670-5p had high level in NSCLC tissues. Dual luciferase reporter assay verified that miR-670-5p was the target of circsSMARCA5, and RBM24 has the binding site of miR-670-5p. Further analysis showed that circsSMARCA5 could negatively regulate miR-670-5p and had positive relationship with RBM24. Moreover, circsSMARCA5 obviously inhibited tumor growth in vivo, reduced cell proliferation and increased cell apoptosis in vitro, while miR-670-5p mimic or RBM24 knockdown could reverse these effects. Thus, circsSMARCA5 may serve as an NSCLC suppressor by regulating the miR-670-5p/RBM24 axis, and it may have the potential to be a biomarker or therapeutic target for NSCLC.

scholarly journals Elevation of EIF4G1 promotes non‐small cell lung cancer progression by activating mTOR signalling

2021 ◽  
Vol 25 (6) ◽  
pp. 2994-3005
Author(s):  
Ying Lu ◽  
Shanshan Yu ◽  
Guangxue Wang ◽  
Zuan Ma ◽  
Xuelian Fu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mtor Signalling

scholarly journals Melatonin Downregulates PD-L1 Expression and Modulates Tumor Immunity in KRAS-Mutant Non-Small Cell Lung Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5649
Author(s):  
Yi-Chun Chao ◽  
Kang-Yun Lee ◽  
Sheng-Ming Wu ◽  
Deng-Yu Kuo ◽  
Pei-Wei Shueng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Tumor Immunity ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Syngeneic Mouse Model

Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC.

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