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 Circular RNA circVAPA contributes to non-small-cell lung cancer progression via miR-342-3p-dependent regulation of ZEB2

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaoyang Liu ◽  
Yang Cheng ◽  
Yan Wang ◽  
Yinhong Zhang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Small Cell Lung

Abstract Background Accumulating evidence demonstrated that circular RNAs (circRNAs) play pivotal regulatory roles in the pathology of cancers. Disclosing the roles and molecular mechanisms of circRNAs in tumorigenesis and development is essential to identify novel diagnostic and therapeutic targets. In this study, we explored the role of circVAPA in non-small-cell lung cancer (NSCLC) progression and its associated mechanism. Methods The expression level of RNA was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was assessed by MTT assay and colony-forming assay. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were assessed by transwell assays. Dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays were used to test the intermolecular interactions. The role of circVAPA was assessed in vivo. And xenograft tumor tissues were analyzed by immunohistochemistry (IHC) staining. Results CircVAPA expression was upregulated in NSCLC tissues and cell lines, and a high level of circVAPA was associated with a poor prognosis of NSCLC patients. CircVAPA silencing suppressed the proliferation, migration, and invasion and induced the apoptosis of NSCLC cells. CircVAPA served as a molecular sponge for microRNA-342-3p (miR-342-3p). miR-342-3p interference largely reversed circVAPA knockdown-mediated anti-tumor effects in NSCLC cells. Zinc finger E-box-binding homeobox 2 (ZEB2) was a target of miR-342-3p, and miR-342-3p overexpression suppressed the malignant behaviors of NSCLC cells largely by downregulating ZEB2. CircVAPA silence repressed xenograft tumor growth in vivo, and IHC assay confirmed that circVAPA silence restrained the proliferation and metastasis but induced the apoptosis of NSCLC cells in vivo. Conclusion CircVAPA contributes to the progression of NSCLC by binding to miR-342-3p to upregulate ZEB2. CircVAPA/miR-342-3p/ZEB2 axis might be a novel potential target for NSCLC treatment.

scholarly journals Circ_0005962 functions as an oncogene to aggravate non-small cell lung cancer progression via circ_0005962/miR-382-5p/PDK4 regulatory network

2020 ◽  
Author(s):  
Zhihong Zhang ◽  
Zhenxiu Shan ◽  
Rubin Chen ◽  
Xiaorong Peng ◽  
Bin Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung

AbstractNon-small cell lung cancer (NSCLC) is a leading threat to human lives with high incidence and mortality. Circular RNAs (circRNAs) were reported to play important roles in human cancers. The purpose of this study was to investigate the role of circ_0005962 and explore the underlying functional mechanisms. The expression of circ_0005962, miR-382-5p and pyruvate dehydrogenase kinase 4 (PDK4) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and cell apoptosis were assessed by cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The protein levels of Beclin 1, light chain3 (LC3-II/LC3-I), PDK4, Cleaved Caspase 3 (C-caspase 3) and proliferating cell nuclear antigen (PCNA) were examined using western blot analysis. Glycolysis was determined according to the levels of glucose consumption and lactate production. The interaction between miR-382-5p and circ_0005962 or PDK4 was predicted by the online tool CircInteractome or starbase and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft model was constructed to investigate the role of circ_0005962 in vivo. circ_0005962 expressed with a high level in NSCLC tissues and cells. Circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but promoted apoptosis in NSCLC cells. MiR-382-5p was targeted by circ_0005962, and its inhibition reversed the role of circ_0005962 knockdown. Besides, PDK4, a target of miR-382-5p, was regulated by circ_0005962 through miR-382-5p, and its overexpression abolished the effects of miR-382-5p reintroduction. Circ_0005962 knockdown suppressed tumor growth in vivo. Circ_0005962 knockdown restrained cell proliferation, autophagy, and glycolysis but stimulated apoptosis through modulating the circ_0005962/miR-382-5p/PDK4 axis. Our study broadened the insights into understanding the mechanism of NSCLC progression.

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.

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 MiR-376a inhibits non-small cell lung cancer cell progression by regulating Rab1A

2019 ◽  
Author(s):  
Zheng-Hao Cao ◽  
Jing-Liang Cheng ◽  
Xian-Zhao Zheng ◽  
Qing-Qing Lv ◽  
Jin-Xin Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Crucial Role ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Post transcriptional gene regulation of microRNA-376a (miR-376a) plays a crucial role for tumorigenesis and cancer development. However, the potential role of miR-367a in non-small cell lung cancer (NSCLC) remains unclear. In this study, we investigated the crucial role of miR-376a in NSCLC by analyzing miR-376a expression as well as its target genes. Through overexpression strategies, we uncovered the molecular mechanisms underlying miR-376a-mediated tumorigenesis. Quantitative real-time PCR analysis demonstrated miR-376a levels to be significantly decreased in NSCLC cells compared with non-tumorigenic counterparts. Interestingly, miR-376a overexpression potentially repressed NSCLC cell proliferation, migration, and invasion, but increased apoptosis in A549 cells. Using bioinformatic approaches, we predicted that miR-376a targets Rab1A, and further luciferase fusion assay demonstrated Rab1A was a direct target of miR-376a and miR-376a inhibited cell proliferation by regulating the mRNA and protein levels of Rab1A in NSCLC cells. Overall, our findings uncover the miR-376a could suppress NSCLC cells progression via directly targeting Rab1A.

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.

scholarly journals LncRNA SNHG19 Promotes the Development of Non-Small Cell Lung Cancer via Mediating miR-137/E2F7 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Guang-Yin Zhao ◽  
Zhao-Feng Ning ◽  
Rui Wang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Cancer Tissues

ObjectiveNon-small cell lung cancer (NSCLC) is a common malignant tumor, which has high incidence and low the 5-year survival rate. Long non-coding RNAs (lncRNAs) play critical roles in carcinoma occurrence and metastasis. Herein, our aim was to investigate the effects of lncRNA SNHG19 in NSCLC progression.Materials and MethodsLong non-coding RNA Small Nucleolar RNA Host Gene 19 (lncRNA SNHG19) expression level was measured by bioinformatics and qRT-PCR. Edu, Transwell, and scratch assays were performed to explore the role of si-SNHG19 or SNHG19 on NSCLC progression. Luciferase assay was used to verify the relationship between SNHG19/E2F7 and miR-137. The experiment of Xenograft was used for exploring the function of SNHG19 in vivo.ResultsSNHG19 was upregulated in cancer tissues, patients plasma and cell lines of NSCLC. Knockdown of SNHG19 inhibited cell proliferation, migration, and invasion. Luciferase assay confirmed that SNHG19 regulated E2F7 expression via interacting with miR-137. Overexpression of SNHG19 accelerated NSCLC tumor progression via miR-137/E2F7 axis both in vitro and in vivo.ConclusionsOur results clarified the SNHG19 function for the first time, and SNHG19 promoted the progression of NSCLC, which was mediated by the miR-137/E2F7 axis. This study might provide new understanding and targets for NSCLC diagnosis and treatment.

High-mobility group box 3 (HMGB3) silencing inhibits non-small cell lung cancer development through regulating Wnt/β-catenin pathway

2020 ◽  
Vol 401 (10) ◽  
pp. 1191-1198 ◽  
Author(s):  
Yunjing Li ◽  
Yongfu Ma ◽  
Tong Zhang ◽  
Changjiang Feng ◽  
Yang Liu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
High Mobility ◽  
Small Cell ◽  
High Mobility Group ◽  
Migration And Invasion ◽  
Small Cell Lung

AbstractIt has been reported that high-mobility group box 3 is overexpressed in various cancers. This study aimed to explore its function in non-small cell lung cancer (NSCLC). A546 and H460 cell lines were used for in vivo experiments, scratch healing tests, transwell migration and invasion experiments. It was first found that HMGB3 was highly expressed in tumor tissues in the patients and associated with NSCLC stage. Silencing of HMGB3 significantly slowed the growth, proliferation and invasion of NSCLC in vitro, and repressed cell growth in vivo. Mechanistic studies suggest that the observed effects were mediated by inhibiting the expression of β-catenin/MMP7/c-Myc in Wnt pathway. Our study highlights the role of HMGB3 in NSCLC, which may provide a therapeutic target for the treatment of NSCLC.

scholarly journals KLF5-induced BBOX1-AS1 contributes to cell malignant phenotypes in non-small cell lung cancer via sponging miR-27a-5p to up-regulate MELK and activate FAK signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jiang Shi ◽  
Chao Yang ◽  
Jinlu An ◽  
Dexun Hao ◽  
Cong Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Function ◽  
Small Cell ◽  
Small Cell Lung ◽  
Gene And Protein Expression

Abstract Background Non-small cell lung cancer (NSCLC) is a major histological subtype of lung cancer with high mortality and morbidity. A substantial amount of evidence demonstrates long non-coding RNAs (lncRNA) as critical regulators in tumorigeneis and malignant progression of human cancers. The oncogenic role of BBOX1 anti-sense RNA 1 (BBOX1-AS1) has been reported in several tumors. As yet, the potential functions and mechanisms of BBOX1-AS1 in NSCLC are obscure. Methods The gene and protein expression was detected by qRT-PCR and western blot. Cell function was determined by CCK-8, colony forming, would healing and transwell assays. Bioinformatics tools, ChIP assays, dual luciferase reporters system and RNA pull-down experiments were used to examine the interaction between molecules. Subcutaneous tumor models in nude mice were established to investigate in vivo NSCLC cell behavior. Results BBOX1-AS1 was highly expressed in NSCLC tissues and cells. High BBOX1-AS1 expression was associated with worse clinical parameters and poor prognosis. BBOX1-AS1 up-regulation was induced by transcription factor KLF5. BBOX1-AS1 deficiency resulted in an inhibition of cell proliferation, migration, invasion and EMT in vitro. Also, knockdown of BBOX1-AS1 suppressed NSCLC xenograft tumor growth in mice in vivo. Mechanistically, BBOX1-AS1 acted act as a competetive “sponge” of miR-27a-5p to promote maternal embryonic leucine zipper kinase (MELK) expression and activate FAK signaling. miR-27a-5p was confirmed as a tumor suppressor in NSCLC. Moreover, BBOX1-AS1-induced increase of cell proliferation, migration, invasion and EMT was greatly reversed due to the overexpression of miR-27a-5p. In addition, the suppressive effect of NSCLC progression owing to BBOX1-AS1 depletion was abated by the up-regulation of MELK. Consistently, BBOX1-AS1-mediated carcinogenicity was attenuated in NSCLC after treatment with a specific MELK inhibitor OTSSP167. Conclusions KLF5-induced BBOX1-AS1 exerts tumor-promotive roles in NSCLC via sponging miR-27a-5p to activate MELK/FAK signaling, providing the possibility of employing BBOX1-AS1 as a therapeutic target for NSCLC patients.

scholarly journals Tumor-associated calcium signal transducer 2 regulates neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769432 ◽  
Author(s):  
Xiaobin Guo ◽  
Xiaoming Zhu ◽  
Limin Zhao ◽  
Xiao Li ◽  
Dongjun Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Calcium Signal ◽  
Small Cell Lung

Lung cancer, especially the non-small-cell lung cancer, is a highly aggressive vascular cancer with excessively activated signaling pathways. Tumor-associated calcium signal transducer 2, also known as trop2, was identified to be correlated with tumor proliferation and invasion of non-small-cell lung cancer; however, the biological role of trop2 in neovascularization of non-small-cell lung cancer remained elusive. In this study, we first verified that trop2 was overexpressed in non-small-cell lung cancer tissues as well as cell lines and that the increased expression of trop2 promoted non-small-cell lung cancer cell proliferation and invasion. Then, we expanded the biological role of trop2 by in vitro and in vivo angiogenesis assay. The tubular formation analysis revealed that trop2 promoted non-small-cell lung cancer angiogenesis in vitro, and the immunohistochemistry staining of vascular markers (CD31 and CD34) provided evidences that trop2 promoted in vivo neovascularization. The results of polymerase chain reaction array revealed that trop2 promoted the expression level of two well-known angiogenesis factors MMP13 and PECAM1. By screening the trop2-related signaling pathways, we observed that excessive angiogenesis was correlated with activation of ERK1/2 signaling pathway, and ERK1/2 inhibitor (U0126) could suppress the tubular formation ability induced by trop2 expression. These results suggested that trop2 facilitated neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway. Targeting trop2 might provide novel anti-angiogenesis strategy for non-small-cell lung cancer treatment.

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