scholarly journals CircRNA circ_0006677 Inhibits the Progression and Glycolysis in Non–Small-Cell Lung Cancer by Sponging miR-578 and Regulating SOCS2 Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Bo Yang ◽  
Fang Zhao ◽  
Lei Yao ◽  
Zhenfeng Zong ◽  
Li Xiao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Circular Rnas ◽  
Small Cell Lung ◽  
Normal Tissues ◽  
Lower Expression

Objective: Circular RNAs (circRNAs) have been demonstrated in playing an important role in the physiological and pathological processes (such as cancer). This paper aims to clarify the role of Circ_0006677 in non–small-cell lung cancer (NSCLC) progression.Methods: Using clinical data and in vitro cell line models, we revealed the tumor-suppressive role of circ_0006677 in lung cancer. Using the online bioinformatics tool, we predicted the target of circ_0006677 and further validated its regulatory mechanisms responsible for its tumor suppressor function in NSCLC.Results: Circ_0006677 expression was reduced in NSCLC tissues of patients and lung cancer cells in comparison to adjacent normal tissues. Lower expression of circ_0006677 was significantly associated with poorer patient survival. Overexpression of circ_0006677 significantly inhibited the ability of NSCLC cell proliferation, migration, invasion, and glycolysis. Mechanically, circ_0006677 could inhibit NSCLC progression and glycolysis by regulating the expression of the signal transducer inhibitor SOSC2 through sponging microRNA-578 (miR-578).Conclusion: Circ_0006677 prevents the progression of NSCLC via modulating the miR-578/SOSC2 axis.

Biological functions of long noncoding RNAs and circular RNAs in small-cell lung cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1751-1763
Author(s):  
Sachin Kumar ◽  
Monu Pandey ◽  
Surender K Sharawat
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Noncoding Rnas ◽  
Cancer Biomarkers ◽  
Small Cell ◽  
Long Noncoding Rnas ◽  
Circular Rnas ◽  
Small Cell Lung

We aim to discuss comprehensively the role of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in small-cell lung cancer (SCLC) biology and their clinical utility as cancer biomarkers. We searched the scientific literature to select articles related to the role of lncRNAs and circRNAs in SCLC biology or as cancer biomarkers. We identified that a number of lncRNAs and circRNAs can regulate key biological processes involved in SCLC development, including cell proliferation, metastasis and chemoresistance mainly acting as miRNA sponges. Also, the expression of a few lncRNAs and circRNAs predicted survival outcome depicting their utility as prognostic biomarkers. Further investigations on the role of lncRNAs and circRNAs in SCLC tumors may yield novel therapeutic targets for SCLC.

scholarly journals An in vitro study to explore the role of prolylcarboxypeptidase in non-small cell lung cancer

BIOCELL ◽  
2020 ◽  
Vol 44 (1) ◽  
pp. 19-26
Author(s):  
Binbin QIAN ◽  
Xiaoduo LIU ◽  
Xiaolin GU ◽  
Lu YANG ◽  
Dake CHEN
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
In Vitro Study ◽  
Small Cell ◽  
Vitro Study ◽  
Small Cell Lung

scholarly journals KPNB1-mediated nuclear translocation of PD-L1 promotes non-small cell lung cancer cell proliferation via the Gas6/MerTK signaling pathway

2020 ◽  
Author(s):  
Wenwen Du ◽  
Jianjie Zhu ◽  
Yuanyuan Zeng ◽  
Ting Liu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung

Abstract In addition to the role of programmed cell death ligand 1 (PD-L1) in facilitating tumour cells escape from immune surveillance, it is considered as a crucial effector in transducing intrinsic signals to promote tumour development. Our previous study has pointed out that PD-L1 promotes non-small cell lung cancer (NSCLC) cell proliferation, but the mechanism remains elusive. Here we first demonstrated that PD-L1 expression levels were positively correlated with p-MerTK levels in patient samples and NSCLC cell lines. In addition, PD-L1 knockdown led to the reduced phosphorylation level of MerTK in vitro. We next showed that PD-L1 regulated NSCLC cell proliferation via Gas6/MerTK signaling pathway in vitro and in vivo. To investigate the underlying mechanism, we unexpectedly found that PD-L1 translocated into the nucleus of cancer cells which was facilitated through the binding of Karyopherin β1 (KPNB1). Nuclear PD-L1 (nPD-L1), coupled with transcription factor Sp1, regulated the synthesis of Gas6 mRNA and promoted Gas6 secretion to activate MerTK signaling pathway. Taken together, our results shed light on the novel role of nPD-L1 in NSCLC cell proliferation and reveal a new molecular mechanism underlying nPD-L1-mediated Gas6/MerTK signaling activation. All above findings provide the possible combinational implications for PD-L1 targeted immunotherapy in the clinic.

Elevated circASCC3 Suppresses Antitumor Immunity by Sponging miR-432-5p to Upregulate C5a in Non-small-cell Lung Cancer

2021 ◽  
Author(s):  
Jian Gao ◽  
Ling-Xian Zhang ◽  
Yong-Qiang Ao ◽  
Chun Jin ◽  
Peng-Fei Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Malignant Phenotype ◽  
In Vivo Models ◽  
Normal Tissues

Abstract Background: Tumor invasion and immune evasion are the main mechanisms underlying the progression of non-small-cell lung cancer (NSCLC). In addition, abnormally expressed circular RNAs (circRNAs) contribute to the malignant phenotype of NSCLC. Thus, further investigation of the mechanism of dysregulated circRNAs may provide new insight into the treatment of NSCLC.Methods: circRNA sequencing was used to explore the different expression profiles of circRNAs in 4 NSCLC tissues and paired normal tissues. Then, the expression of key circRNAs in NSCLC tissues and matched normal tissues was further evaluated via in situ hybridization and in cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). Next, in vitro and in vivo models of NSCLC were employed to uncover the functions and mechanisms of key circRNAs in NSCLC progression and treatment.Results: circASCC3 (hsa_circ_0077495) was overexpressed in NSCLC tissues compared to paired normal tissues, and the upregulation of circASCC3 indicated a dismal prognosis in patients with NSCLC. Overexpressed circASCC3 enhanced the malignant phenotype of NSCLC cells in vitro and led to an immunosuppressive microenvironment in vivo. Mechanistically, circASCC3 sponged miR-432-5p to increase the expression of complement C5a, which induced the progression and dysfunctional immune status of NSCLC. Moreover, the combination of the C5aR inhibitor PMX-53 and anti-programmed cell death 1 (PD-1) antibody achieved synergistic effects in NSCLC models overexpressing circASCC3.Conclusion: These results uncover the contributions of circASCC3 to NSCLC progression and immunosuppression and provide a potential strategy for overcoming resistance to anti-PD-1 therapy.

scholarly journals CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Hang Li ◽  
Jun Che ◽  
Mian Jiang ◽  
Ming Cui ◽  
Guoxing Feng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Estrogen Receptor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Genes ◽  
Small Cell ◽  
Small Cell Lung

Abstract Introduction Radioresistance is a major challenge in lung cancer radiotherapy, and new radiosensitizers are urgently needed. Estrogen receptor β (ERβ) is involved in the progression of non-small cell lung cancer (NSCLC), however, the role of ERβ in the response to radiotherapy in lung cancer remains elusive. In the present study, we investigated the mechanism underlying ERβ-mediated transcriptional activation and radioresistance of NSCLC cells. Methods Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the expression of CLPTM1L, ERβ and other target genes. The mechanism of CLPTM1L in modulation of radiosensitivity was investigated by chromatin immunoprecipitation assay, luciferase reporter gene assay, immunofluorescence staining, confocal microscopy, coimmunoprecipitation and GST pull-down assays. The functional role of CLPTM1L was detected by function assays in vitro and in vivo. Results CLPTM1L expression was negatively correlated with the radiosensitivity of NSCLC cell lines, and irradiation upregulated CLPTM1L in radioresistant (A549) but not in radiosensitive (H460) NSCLC cells. Meanwhile, IR induced the translocation of CLPTM1L from the cytoplasm into the nucleus in NSCLC cells. Moreover, CLPTM1L induced radioresistance in NSCLC cells. iTRAQ-based analysis and cDNA microarray identified irradiation-related genes commonly targeted by CLPTM1L and ERβ, and CLPTM1L upregulated ERβ-induced genes CDC25A, c-Jun, and BCL2. Mechanistically, CLPTM1L coactivated ERβ by directly interacting with ERβ through the LXXLL NR (nuclear receptor)-binding motif. Functionally, ERβ silencing was sufficient to block CLPTM1L-enhanced radioresistance of NSCLC cells in vitro. CLPTM1L shRNA treatment in combination with irradiation significantly inhibited cancer cell growth in NSCLC xenograft tumors in vivo. Conclusions The present results indicate that CLPTM1L acts as a critical coactivator of ERβ to promote the transcription of its target genes and induce radioresistance of NSCLC cells, suggesting a new target for radiosensitization in NSCLC therapy.

scholarly journals A Novel Circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 Pathway Regulates Cisplatin-Resistance in Non-Small Cell Lung Cancer (NSCLC)

2020 ◽  
Author(s):  
Xiang Zhu ◽  
Jing Han ◽  
Huiyin Lan ◽  
Qingren Lin ◽  
Yuezhen Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cisplatin Resistance ◽  
Circular Rna ◽  
Small Cell ◽  
Circular Rnas ◽  
Small Cell Lung

Abstract Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggested that targeting circular RNAs (circRNAs) became an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated. Based on this, this study identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade contributed to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, the parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin stimulation to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells, instead of CS-NSCLC cells. Further experiments validated that hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells. Interestingly, the gain- and loss-function experiments validated that knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating miR-377-3p/GOT1 axis. Furthermore, the xenograft tumor-bearing mice models were established by using the CR-NSCLC cells, and we proved that silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo. In general, analysis of data suggested that targeting hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel agents to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.

Hsa_circ_0003288 facilitates tumor progression by targeting miR-145 in non–small cell lung cancer cells

2021 ◽  
pp. 1-9
Author(s):  
Li-Na Pan ◽  
Yun-Fang Ma ◽  
Jia-An Hu ◽  
Zhi-Hong Xu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Circular RNA (circRNA) has been shown to participate in various tumors, including lung cancer. In the present study, we explored the expression and functional relevance of hsa_circ_0003288 in human non-small cell lung cancer (NSCLC). We verified that hsa_circ_0003288 expression was upregulated in lung cancer tissues and cell lines. Overexpression of hsa_circ_0003288 dramatically promoted lung cancer cell proliferation, colony formation, inhibited apoptosis, and increased cell migration and invasion in vitro. Xenograft experiments showed that hsa_circ_0003288 overexpression accelerated tumor growth in vivo. Mechanistically, hsa_circ_0003288 negatively regulated miR-145 to exert the oncogenic role in lung cancer. Overexpression of miR-145 decreased cell proliferation, induced apoptosis, and suppressed migration and invasion in lung cancer. Additionally, miR-145 co-transfection abolished the oncogenic role of hsa_circ_0003288. Collectively, these findings identified a novel regulatory role of hsa_circ_0003288/miR-145 axis in the progression of NSCLC.

scholarly journals Expression of CDCA7 Is a Prognostic Biomarker and Potential Therapeutic Target in Non-small Cell Lung Cancer 

2021 ◽  
Author(s):  
wen yuan ◽  
Wenhui Zeng ◽  
Haiyan Tan ◽  
Muhammad Jamal ◽  
Tian Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Target ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Tissues

Abstract BackgroundCell Division Cycle Associated 7 (CDCA7) was first identified as a direct target gene of c-Myc and dysregulated in various types of human cancer. However, it has limited implication in non-small Cell Lung Cancer (NSCLC). We aimed to explore the critical role of CDCA7 in NSCLC.Methods In this study, we identified CDCA7 upregulation and association with the prognosis of NSCLC by integrating analysis of 3 Gene Expression Omnibus (GEO) databases. Real-time PCR and immunohistochemistry (IHC) were used to determine collected clinical NSCLC samples. Chi-square test was used to examine possible correlations between CDCA7 expression and clinicopathological factors. Univariate and multivariate Cox proportional hazards regression analysis were performed to determine whether CDCA7 is an independent risk factor for overall survival (OS). The effect of CDCA7 expression on proliferation, cell cycle and apoptosis ability of NSCLC cells was detected by cell counting kit-8 (CCK-8) and flow cytometry. CDCA7 stably knocking down cell line was established and Western blotting assay was applied to measure relevant protein expression. Xenograft models were used to examine the role of CDCA7 on tumorigenicity of NSCLC cells.Results Analysis of clinical samples confirmed the CDCA7 high expression in tumor tissues compared with adjacent non-tumor tissues and predicted shorter OS time. COX proportional risk model analysis showed that the expression levels of CDCA7 was independent prognostic factors. We observed that CDCA7 silencing efficiently affect the proliferation, apoptosis and cycle distribution of NSCLC cells in vitro. Further results demonstrated that the expression of CDCA7 in A549/DDP cells was significantly higher than that in A549 cells, CDCA7 silencing efficiently down regulation cisplatin sensitivity in A549/DDP cells. Importantly, the depletion of CDCA7 strongly reduced the tumorigenicity of NSCLC cells in vivo. Furthermore, depletion of CDCA7 expression markedly affected the expression of cell division protein kinase 6 (CDK6) and caspase7 both in vitro and in vivo. In vitro study, we showed that CDCA7 silencing promotes A549 apoptosis via extracellular regulated protein kinases (ERK) pathway.ConclusionHighly expressed CDCA7 plays a crucial role in the pathogenesis of NSCLC and might be a potential prognostic factor and therapeutic target in NSCLC.

Up-regulated HMGB1 in the pleural effusion of non-small cell lung cancer (NSCLC) patients reduces the chemosensitivity of NSCLC cells

2018 ◽  
Vol 104 (5) ◽  
pp. 338-343 ◽  
Author(s):  
Ying Ma ◽  
Shirong Kang ◽  
Xu Wu ◽  
Bateer Han ◽  
Zhiyong Jin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Background: Pleural effusion is one of the complications of human non-small cell lung cancer (NSCLC). High mobility group box-1 protein (HMGB1) correlates highly with invasion and metastasis in multiple tumors. The aim of this study was to explore the clinical value of HMGB1 in NSCLC patients, and to investigate the role of HMGB1 in the development of pleural effusion. In addition, we also investigated the regulatory role of HMGB1 in the sensitivity of NSCLC cells to cisplatin. Methods: 46 NSCLC malignant pleural effusion (MPE) and 31 benign pleural effusion samples were quantitatively analyzed with Enzyme-Linked Immunosorbent Assay (ELISA) for cytokines, such as IL-1beta, IL-6, IL-8 and HMGB1. The HMGB1 expression in NSCLC tissues was examined with RT-qPCR and western blotting methods. Then the influence by HMGB1 on the chemosensitivity of lung cancer A549 cells was examined with MTT assay and colony forming assay for the A549 cells post the treatment with cisplatin or (and) HMGB1. Results: The results demonstrated that HMGB1 was up-regulated in the pleural effusion of NSCLC patients, along with the up-regulated levels of proinflammatory cytokines such as IL-6 and IL-8. And the up-regulation of HMGB1 was confirmed at both the mRNA and protein levels in the NSCLC tissues. Recombinant HMGB1 reduced the sensitivity of A549 cells to cisplatin in vitro. Conclusions: In conclusion, HMGB1 was up-regulated in the pleural effusion and tumor tissues of NSCLC patients. HMGB1 reduced the sensitivity of NSCLC A549 cells to cisplatin in vitro.

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