scholarly journals Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoju Li ◽  
Shengtian Su ◽  
Dan Ye ◽  
Zhigao Yu ◽  
Wenjing Lu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mice Model ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Abstract Background Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown. Methods The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo. Results We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1. Conclusion Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.

scholarly journals Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Fu-Tao Chen ◽  
Fu-Kuan Zhong
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Tumor Growth And Metastasis

Objective. To determine the expression levels of KIF18A in lung adenocarcinoma and its relationship with the clinicopathologic features of patients undergoing radical colectomy and explore the potential role in the progression of lung adenocarcinoma. Methods. Immunohistochemical assays were performed to explore the expression levels of KIF18A in 82 samples of lung adenocarcinoma and corresponding normal tissues. According to the levels of KIF18A expression in lung adenocarcinoma tissue samples, patients were classified into the KIF18A high expression group and low expression group. Clinical data related to the perioperative clinical features (age, gender, smoking, tumor size, differentiation, clinical stage, and lymph node metastasis), the potential correlation between KIF18A expression levels, and clinical features were analyzed, and the effects of KIF18A on lung adenocarcinoma cell proliferation, migration, and invasion were measured by colony formation assay, MTT assay, wound healing assay, and transwell assays. The possible effects of KIF18A on tumor growth and metastasis were measured in mice through tumor growth and tumor metastasis assays in vivo. Results. KIF18A in lung adenocarcinoma tissues. Further, KIF18A was significantly associated to clinical characteristic features including the tumor size (P=0.033) and clinical stage (P=0.041) of patients with lung adenocarcinoma. Our data also investigated that KIF18A depletion dramatically impairs the proliferation, migration, and invasion capacity of lung adenocarcinoma cells in vitro and inhibits tumor growth and metastasis in mice. Conclusions. Our study reveals the involvement of KIF18A in the progression and metastasis of lung adenocarcinoma and provides a novel therapeutic target for the treatment of lung adenocarcinoma.

scholarly journals RETRACTED ARTICLE: Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma

2016 ◽  
Vol 7 (9) ◽  
pp. e2388-e2388 ◽  
Author(s):  
Shuang Wei ◽  
Zun-yi Zhang ◽  
Sheng-ling Fu ◽  
Jun-gang Xie ◽  
Xian-sheng Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Adenocarcinoma Cell ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Abstract Our previous study revealed that Ku80 was overexpressed in lung cancer tissues and hsa-miR-623 regulated the Ku80 expression; however, the detailed function of hsa-miR-623 in lung cancer was unclear. We identified that hsa-miR-623 bound to the 3'-UTR of Ku80 mRNA, thus significantly decreasing Ku80 expression in lung adenocarcinoma cells. Hsa-miR-623 was downregulated in lung adenocarcinoma tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Downregulation of hsa-miR-623 was associated with poor clinical outcomes of lung adenocarcinoma patients. Hsa-miR-623 suppressed lung adenocarcinoma cell proliferation, clonogenicity, migration and invasion in vitro. Hsa-miR-623 inhibited xenografts growth and metastasis of lung adenocarcinoma in vivo. Ku80 knockdown in lung adenocarcinoma cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-623 overexpression. Further, hsa-miR-623 overexpression decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression levels, with decreased ERK/JNK phosphorylation. Inhibition of hsa-miR-623 or overexpression of Ku80 promoted lung adenocarcinoma cell invasion, activated ERK/JNK phosphorylation and increased MMP-2/9 expressions, which could be reversed by ERK kinase inhibitor or JNK kinase inhibitor. In summary, our results showed that hsa-miR-623 was downregulated in lung adenocarcinoma and suppressed the invasion and metastasis targeting Ku80 through ERK/JNK inactivation mediated downregulation of MMP-2/9. These findings reveal that hsa-miR-623 may serve as an important therapeutic target in lung cancer therapy.

scholarly journals Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Jingpeng Wang ◽  
Shuyuan Li ◽  
Gaofeng Zhang ◽  
Huihua Han
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Volatile Anesthetic ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas

Abstract Background Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression. Methods The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay. Results Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo. Conclusion Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.

scholarly journals PD-L1 lncRNA splice promotes lung adenocarcinoma progression via enhancing c-Myc activity

2020 ◽  
Author(s):  
Shuang Qu ◽  
Zichen Jiao ◽  
Geng Lu ◽  
Bing Yao ◽  
Ting Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Great Promise ◽  
Non Coding Rna ◽  
Adenocarcinoma Cells ◽  
T Cell Immune Responses ◽  
Lung Adenocarcinoma Cells ◽  
Novel Strategy ◽  
L1 Protein

ABSTRACTAlthough blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the efficacy of such immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism underlying the limited efficacy of PD-L1 inhibitors remains unclear. Here, we show that human lung adenocarcinoma, regardless of PD-L1 protein positive or negative, all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) via alternative splicing, which promotes lung adenocarcinoma proliferation and metastasis. PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ in a manner similar to PD-L1 mRNA. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc directly binds to c-Myc and enhances c-Myc transcriptional activity downstream in lung adenocarcinoma cells. Our results provide targeting PD-L1-lnc−c-Myc axis as a novel strategy for lung cancer therapy.

scholarly journals The TWIST1-centered competing endogenous RNA network promotes proliferation, invasion, and migration of lung adenocarcinoma

Oncogenesis ◽  
2019 ◽  
Vol 8 (11) ◽  
Author(s):  
Wenjie Xia ◽  
Qixing Mao ◽  
Bing Chen ◽  
Lin Wang ◽  
Weidong Ma ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Invasion And Migration ◽  
Non Coding Rnas ◽  
And Migration

Abstract The proposed competing endogenous RNA (ceRNA) mechanism suggested that diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs could communicate with each other by competing for binding to shared microRNAs. The ceRNA network (ceRNET) is involved in tumor progression and has become a hot research topic in recent years. To date, more attention has been paid to the role of non-coding RNAs in ceRNA crosstalk. However, coding transcripts are more abundant and powerful than non-coding RNAs and make up the majority of miRNA targets. In this study, we constructed a mRNA-mRNA related ceRNET of lung adenocarcinoma (LUAD) and identified the highlighted TWIST1-centered ceRNET, which recruits SLC12A5 and ZFHX4 as its ceRNAs. We found that TWIST1/SLC12A5/ZFHX4 are all upregulated in LUAD and are associated with poorer prognosis. SLC12A5 and ZFHX4 facilitated proliferation, migration, and invasion in vivo and in vitro, and their effects were reversed by miR-194–3p and miR-514a-3p, respectively. We further verified that SLC12A5 and ZFHX4 affected the function of TWIST1 by acting as ceRNAs. In summary, we constructed a mRNA-mRNA related ceRNET for LUAD and highlighted the well-known oncogene TWIST1. Then we verified that SLC12A5 and ZFHX4 exert their oncogenic function by regulating TWIST1 expression through a ceRNA mechanism.

scholarly journals C/EBPα Suppresses Lung Adenocarcinoma Cell Invasion and Migration by Inhibiting β-Catenin

2017 ◽  
Vol 42 (5) ◽  
pp. 1779-1788 ◽  
Author(s):  
Jinchang Lu ◽  
Chunling Du ◽  
Junxia Yao ◽  
Bo Wu ◽  
Yanhong Duan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Lung Adenocarcinoma ◽  
Cell Invasion ◽  
Migration And Invasion ◽  
Adenocarcinoma Cell ◽  
Invasion And Migration ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
And Migration

Background/Aims: The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is a basic leucine zipper transcription factor that plays essential roles in tumor progression. Although decreased or absent C/EBPα expression in many cancers suggests a possible role for C/EBPα as a tumor suppressor, the functions of C/EBPα in lung adenocarcinoma remain unclear. Methods: Here, C/EBPα expression levels in 26 lung adenocarcinoma and para-carcinoma tissue samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays, wound healing assay and three-dimensional spheroid invasion assay were performed to assess the effects of C/EBPα on migration and invasion in lung adenocarcinoma cells in vitro. Western blotting was applied to analyze the potential mechanisms. Results: C/EBPα was found to be decreased in lung adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of C/EBPα significantly inhibited the migration and invasion of lung adenocarcinoma cells. In addition, C/EBPα overexpression suppressed the epithelial–mesenchymal transition (EMT) that was characterized by a gain of epithelial and loss of mesenchymal markers. Further study showed that C/EBPα suppressed the transcription of β-catenin and downregulated the levels of its downstream targets. Conclusion: Our data suggest that C/EBPα inhibits lung adenocarcinoma cell invasion and migration by suppressing β-catenin-mediated EMT in vitro. Thus, C/EBPα may be helpful as a potential target for treatment of lung adenocarcinoma.

scholarly journals Circ_0001367 inhibits glioma proliferation, migration and invasion by sponging miR-431 and thus regulating NRXN3

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Liang Liu ◽  
Peng Zhang ◽  
Xuchen Dong ◽  
Haoran Li ◽  
Suwen Li ◽  
...  
Keyword(s):  
Close Correlation ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Dependent Manner ◽  
Glioma Growth

AbstractMany studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.

scholarly journals hsa_circ_0023409 Accelerates Gastric Cancer Cell Growth and Metastasis Through Regulating the IRS4/PI3K/AKT Pathway

2021 ◽  
Vol 30 ◽  
pp. 096368972097539
Author(s):  
Jian Li ◽  
Yongjing Yang ◽  
Dequan Xu ◽  
Ling Cao
Keyword(s):  
Gastric Cancer ◽  
Histological Grade ◽  
Human Life ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Circular Rnas

Gastric cancer (GC) is a big threat to human life and health. Circular RNAs (circRNAs), a subclass of noncoding RNAs, were reported to play a critical role in GC progression. Here, we investigated the role of a novel circRNA named hsa_circ_0023409 in GC and its mechanism. Hsa_circ_0023409 expression in GC and adjacent tissues was examined by quantitative real-time polymerase chain reaction and in situ hybridization. The functions of hsa_circ_0023409 in GC cells were assessed both in vitro and in vivo. Immunofluorescence staining was performed for the localization of hsa_circ_0023409 and miR-542-3p in cells. The interaction between hsa_circ_0023409 and miR-542-3p, and miR-542-3p and insulin receptor substrate 4 (IRS4) was detected by dual-luciferase reporter assay. The effect of hsa_circ_0023409, miR-542-3p, and IRS4 on IRS4/phosphatidylinositol 3-kinase (PI3K)/AKT pathway was detected by western blot. The results showed that hsa_circ_0023409 was mainly located in cytoplasm and highly expressed in GC tissues and cells. Moreover, hsa_circ_0023409 showed positive correlation with tumor size, histological grade, and tumor–node–metastasis staging of GC patients. Functional studies showed that hsa_circ_0023409 promoted cell viability, proliferation, migration, and invasion and suppressed apoptosis in GC. Mechanism studies demonstrated that hsa_circ_0023409 upregulated IRS4 via sponging miR-542-3p in GC cells. Furthermore, IRS4 overexpression activated the PI3K/AKT pathway and reversed the inhibitory effect of hsa_circ_0023409 knockdown on the PI3K/AKT pathway. Taken together, we prove that hsa_circ_0023409 activates IRS4/PI3K/AKT pathway by acting as a sponge for miR-542-3p, thus promoting GC progression, indicating that hsa_circ_0023409 may serve as a potential target for treatment of GC and prognosis of GC patients.

scholarly journals CircKEAP1 serves as a ceRNA to suppress lung adenocarcinoma progression by activating KEAP1 signal pathway

2020 ◽  
Author(s):  
Yanbo Wang ◽  
Fenghai Ren ◽  
Dawei Sun ◽  
Jing Liu ◽  
BenKun Liu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Expression Profiles ◽  
Signal Pathway ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Tumor Tissues ◽  
Rna Immunoprecipitation

Abstract BackgroundCircular RNAs (circRNAs) are widely expressed noncoding RNAs, and plays a key role in the biological function of competitive endogenous RNA (ceRNA) network in various human diseases, especially in cancer. However, the regulatory roles of circRNAs in lung adenocarcinoma (LUAD) remains largely unknown. MethodsThe expression profiles of circRNAs in LUAD tissues and adjacent non-tumor tissues were analyzed by Agilent Arraystar Human CircRNA microarray. The level and prognostic values of circKEAP1 in tissues and cancer cell lines were determined by quantitative real-time PCR. Then, the effects of circKEAP1 on tumor growth were investigated by functional experiments in vitro and in vivo. Mechanistically, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between circKEAP1 and miR-141-3p in LUAD.ResultsWe found circKEAP1 was significantly downregulated in LUAD tissues, and repressed tumor growth both in vitro and in vivo. Mechanistically, circKEAP1 competitively binds to miR-141-3p and relive miR-141-3p repression for its target gene KEAP1, which activated the KEAP1/NRF2 signal pathway, and finally suppress the cell proliferation.ConclusionsOur findings suggest that circKEAP1 inhibits LUAD progression through circKEAP1/miR-141-3p/KEAP1 axis and it may serve as a new target for treatment of LUAD patients.

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