scholarly journals circFADS2 regulates lung cancer cells proliferation and invasion via acting as a sponge of miR-498

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Fucheng Zhao ◽  
Yanru Han ◽  
Zhenzhou Liu ◽  
Zhenxia Zhao ◽  
Zhuoran Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Nonsmall Cell Lung Cancer ◽  
Lung Cancer Cells ◽  
Tumor Promoter ◽  
In Vitro Assays ◽  
Luciferase Reporter ◽  
Proliferation And Invasion

CircRNAs could play critical functions in tumor progression. However, the expression and underlying mechanism of circRNAs in lung cancer progression remain poorly defined. In the present study, high-throughput microarray assay revealed that hsa_circRNA_100833 (identified as circFADS2) was markedly evaluated in lung cancer tissues, and it was further validated by qRT-PCR. High expression of circFADS2 was correlated with advanced TNM stage, lymph node metastasis, poor differentiation, and shorter overall survival of NSCLC patients. In vitro assays results showed that circFADS2 inhibition suppressed lung cancer cells proliferation and invasion ability. Bioinformatics analysis showed that miR-498 contained the complementary binding region of circFADS2, which was confirmed by Dual-luciferase reporter assay. In addition, the expression of miR-498 was down-regulated and negatively associated with circFADS2 expression in nonsmall cell lung cancer. Furthermore, rescue assays showed that miR-498 inhibitors abolished the effects of circFADS2 inhibition on lung cancer cells progression. Taken together, our findings indicated that circFADS2 was an effective tumor promoter in lung cancer progression, and its functions were performed by regulating the expression of miR-498. These data suggested that circFADS2 could act as a target for lung cancer treatment.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

scholarly journals POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

scholarly journals Rhophilin-2 Upregulates Glutamine Synthetase by Stabilizing c-Myc Protein and Confers Resistance to Glutamine Deprivation in Lung Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Dakai Xiao ◽  
Jiaxi He ◽  
Zhihua Guo ◽  
Huiming He ◽  
Shengli Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Glutamine Synthetase ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Clinical Sample ◽  
Glutamine Metabolism ◽  
Lung Cancer Cells ◽  
Mesenchymal Transformation ◽  
Proliferation And Invasion

IntroductionRHPN2, a member of rhophilin family of rho-binding proteins, regulates actin cytoskeleton and vesicular trafficking, and promotes mesenchymal transformation in cancer. We have found that RHPN2 was significantly mutated in lung adenocarcinoma (LUAD). However, the role of RHPN2 in lung cancer is not fully understood.MethodsIn the present study, we investigated the expression of RHPN2 in 125 patients with LUAD by qRT-PCR and correlated its expression with clinical characteristics. The effects of RHPN2 on the proliferation and invasion of lung cancer cells were determined by CCK-8 and in vitro transwell assays, clonogenic assay, and xenograft mouse model. The RhoA pull down assay and Western blotting were performed to elucidate the mechanism of RNPN2 in tumorigenesis of lung cancer.ResultsRHPN2 was overexpressed in tumors from LUAD, and high levels of RHPN2 were associated with poor prognosis of LUAD patients. RHPN2 was required for proliferation and invasion of lung cancer cells. Intriguingly, overexpression of RHPN2 conferred the resistance to glutamine depletion in lung cancer cells. Mechanistic studies revealed that ectopic overexpression of RHPN2 promoted the stability of c-Myc protein via phosphorylation at Ser62 and increased c-Myc target glutamine synthetase (GS). Analysis of GS expression in clinical sample showed that the expression of GS was elevated in tumor cells. Kaplan-Meier analysis revealed that high levels of GS were significantly associated with worse overall survival time of the patients with LUAD.ConclusionsTaken together, this study suggested that RHPN2 was involved in tumorigenesis of lung cancer via modulating c-Myc stability and the expression of its target GS in lung adenocarcinoma, which links RHPN2 and glutamine metabolism.

scholarly journals Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Juze Yang ◽  
Qiongzi Qiu ◽  
Xinyi Qian ◽  
Jiani Yi ◽  
Yiling Jiao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Small Gtpase ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Rna Seq ◽  
Lung Carcinogenesis ◽  
Cancer Tissues

Abstract Introduction Long noncoding RNAs (lncRNAs) are emerging as key players in the development and progression of cancer. However, the biological role and clinical significance of most lncRNAs in lung carcinogenesis remain unclear. In this study, we identified and explored the role of a novel lncRNA, lung cancer associated transcript 1 (LCAT1), in lung cancer. Methods We predicted and validated LCAT1 from RNA-sequencing (RNA-seq) data of lung cancer tissues. The LCAT1–miR-4715-5p–RAC1 axis was assessed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Signaling pathways altered by LCAT1 knockdown were identified using RNA-seq. Furthermore, the mechanism of LCAT1 was investigated using loss-of-function and gain-of-function assays in vivo and in vitro. Results LCAT1 is an oncogene that is significantly upregulated in lung cancer tissues and associated with poor prognosis. LCAT1 knockdown caused growth arrest and cell invasion in lung cancer cells in vitro, and inhibited tumorigenesis and metastasis in the mouse xenografts. Mechanistically, LCAT1 functions as a competing endogenous RNA for miR-4715-5p, thereby leading to the upregulation of the activity of its endogenous target, Rac family small GTPase 1 (RAC1). Moreover, EHop-016, a small molecule inhibitor of RAC1, as an adjuvant could improve the Taxol monotherapy against lung cancer cells in vitro. Conclusions LCAT1–miR-4715-5p–RAC1/PAK1 axis plays an important role in the progression of lung cancer. Our findings may provide valuable drug targets for treating lung cancer. The novel combination therapy of Taxol and EHop-016 for lung cancer warrants further investigation, especially in lung cancer patients with high LCAT1 expression.

MiR-302a-3p, Sponged by HOXA-AS2, Suppresses Cell Proliferation and Invasion in Lung Cancer Cells

2019 ◽  
Vol 9 (12) ◽  
pp. 1644-1652
Author(s):  
Xueqin Pan ◽  
Dongchun Ma
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
Lung Cancer Cells ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion

Lung cancer is one of the most common malignant cancers with a poor survival rate and high mortality worldwide. MiRNAs have been evaluated as crucial regulators of human gene expression, and exerted vital role involved in cancer progression. MiR-302a-3p was aberrant expressed in cancers that include pancreatic cancer and hepatocellular cancer, but its biological role in lung cancer remains elusive. This study aimed to discover the role and potential mechanism of miR-302a-3p in lung cancer. The lung cancer cell line with the highest expression of miR-302a-3p was selected, which was then subjected to transfection of miR-302a-3p mimic. Quantitative RT-PCR was performed to detect gene expression. Western blot assay was performed to determine corresponding genes that related to cell proliferation, apoptosis and invasion. Cell Counting Kit (CCK)-8 assay, flow cytometry analysis, wound healing and Transwell assay were performed to detect cell proliferation, apoptosis, migration and invasion, respectively. Luciferase reporter assay was carried out to identify the targeting relationship of miR-302-3p and HOXA-AS2. MiR-302a-3p was downregulated in lung cancer cells, and overexpression of miR-302a-3p significantly suppressed cell proliferation, migration, invasion and promoted cell apoptosis. HOXA-AS2 was a direct target of miR-302a-3p and was regulated by miR-302a-3p. HOXA-AS2 was upregulated in lung cancer cells. Upregulated HOXA-AS2 could reverse the effect that overexpression of miR-302a-3p caused on cell proliferation, apoptosis, migration and invasion. Overall, miR-302a-3p exhibited anti-oncogenic activity by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis in lung cancer by targeting HOXA-AS2, disclosing the role and regulatory mechanism of miR-302a-3p, which provided a promising therapeutic target for the clinical application of lung cancer treatment.

scholarly journals FOXH1 promotes lung cancer progression by activating the Wnt/β-catenin signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Zhang ◽  
Xian Zhang ◽  
Shasha Yang ◽  
Yanqiu Bao ◽  
Dongyuan Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Mesenchymal Transition

Abstract Background The expression of forkhead box protein H1 (FOXH1) is frequently upregulated in various cancers. However, the molecular mechanisms underlying the association between FOXH1 expression and lung cancer progression still remain poorly understood. Thus, the main objective of this study is to explore the role of FOXH1 in lung cancer. Methods The Cancer Genome Atlas dataset was used to investigate FOXH1 expression in lung cancer tissues, and the Kaplan–Meier plotter dataset was used to determine the role of FOXH1 in patient prognosis. A549 and PC9 cells were transfected with short hairpin RNA targeting FOXH1 mRNA. The Cell Counting Kit-8, colony formation, soft agar, wound healing, transwell invasion and flow cytometry assays were performed to evaluate proliferation, migration and invasion of lung cancer cells. Tumorigenicity was examined in a BALB/c nude mice model. Western blot analysis was performed to assess the molecular mechanisms, and β-catenin activity was measured by a luciferase reporter system assay. Results Higher expression level of FOXH1 was observed in tumor tissue than in normal tissue, and this was associated with poor overall survival. Knockdown of FOXH1 significantly inhibited lung cancer cell proliferation, migration, invasion, and cycle. In addition, the mouse xenograft model showed that knockdown of FOXH1 suppressed tumor growth in vivo. Further experiments revealed that FOXH1 depletion inhibited the epithelial-mesenchymal transition of lung cancer cells by downregulating the expression of mesenchymal markers (Snail, Slug, matrix metalloproteinase-2, N-cadherin, and Vimentin) and upregulating the expression of an epithelial marker (E-cadherin). Moreover, knockdown of FOXH1 significantly downregulated the activity of β-catenin and its downstream targets, p-GSK-3β and cyclin D1. Conclusion FOXH1 exerts oncogenic functions in lung cancer through regulation of the Wnt/β-catenin signaling pathway. FOXH1 might be a potential therapeutic target for patients with certain types of lung cancer.

scholarly journals The intrinsic role and mechanism of tumor expressed-CD38 on lung adenocarcinoma progression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Long Gao ◽  
Yuan Liu ◽  
Xiaohong Du ◽  
Sai Ma ◽  
Minmin Ge ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Enzymatic Activity ◽  
Lung Adenocarcinoma ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
In Vitro Assays ◽  
Knock Out

AbstractIt has been recently reported that CD38 expressed on tumor cells of multiple murine and human origins could be upregulated in response to PD-L1 antibody therapy, which led to dysfunction of tumor-infiltrating CD8+ T immune cells due to increasing the production of adenosine. However, the role of tumor expressed-CD38 on neoplastic formation and progression remains elusive. In the present study, we aimed to delineate the molecular and biochemical function of the tumor-associated CD38 in lung adenocarcinoma progression. Our clinical data showed that the upregulation of tumor-originated CD38 was correlated with poor survival of lung cancer patients. Using multiple in vitro assays we found that the enzymatic activity of tumor expressed-CD38 facilitated lung cancer cell migration, proliferation, colony formation, and tumor development. Consistently, our in vivo results showed that inhibition of the enzymatic activity or antagonizing the enzymatic product of CD38 resulted in the similar inhibition of tumor proliferation and metastasis as CD38 gene knock-out or mutation. At biochemical level, we further identified that cADPR, the mainly hydrolytic product of CD38, was responsible for inducing the opening of TRPM2 iron channel leading to the influx of intracellular Ca2+ and then led to increasing levels of NRF2 while decreasing expression of KEAP1 in lung cancer cells. These findings suggested that malignant lung cancer cells were capable of using cADPR catalyzed by CD38 to facilitate tumor progression, and blocking the enzymatic activity of CD38 could be represented as an important strategy for preventing tumor progression.

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