scholarly journals IGF2BP3 Promotes Lung Cancer Progression Through FTO Dependent m6A Modification by Stabilizing N-myc

2020 ◽  
Author(s):  
Xiaolin Wang ◽  
Yong Chen ◽  
Lingfeng Min ◽  
Hongcan Shi ◽  
Shichun Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Carcinogenesis ◽  
Small Cell Lung ◽  
Western Blots

Abstract Background: N6-methyladenosine modification has been involved in various biological processes. However, its role in non-small cell lung cancer has not been well studied. Here, we show that IGF2BP3, as an transcription factor, plays a critical oncogenic role in non-small-cell lung cancer carcinogenesis through activating FTO expression and inducing aberrant m6A modification. Methods: To evaluate the role of IGF2BP3 in non-small-cell lung cancer, we performed cell proliferation and cell cycle assays in three lung cancer cell lines. Lung cancer mouse model is used to examine the effects of IGF2BP3/FTO/N-myc on lung proliferation potentials in vivo. We analyzed the correlation between IGF2BP3 and FTO, IGF2BP3 and N-myc protein in colon cancer patients by Pearson correlation. To finally explore the relationship of IGF2BP3/FTO/N-myc, we used western blots, proliferation and cell cycle assays to confirm that IGF2BP3 may regulate lung cancer progression through FTO dependent m6A modification by stabilizing N-myc.Results: We first identified that IGF2BP3 overexpressed in non-small-cell lung cancer tissue and cells. Then, we showed that FTO was the dysregulated factor responsible for the abnormal N6-methyladenosine modification in non-small-cell lung cancer. The loss-of-function assay demonstrated that IGF2BP3 enhances FTO-mediated cell proliferation and promotes cell apoptosis, through regulating expression of target gene N-myc by reducing m6A level in mRNA transcript. Conclusion: Our study demonstrates the functional importance of IGF2BP3 and N6-methyladenosine methylation modification in the tumor progression of non-small-cell lung cancer, and provides profound insights into lung carcinogenesis and drug response.

scholarly journals Circ_PIP5K1A regulates cisplatin resistance and malignant progression in non-small cell lung cancer cells and xenograft murine model via depending on miR-493-5p/ROCK1 axis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nan Feng ◽  
Zhi Guo ◽  
Xiaokang Wu ◽  
Ying Tian ◽  
Yue Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Motility ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Mtt Assay ◽  
Small Cell ◽  
Small Cell Lung

Abstract Background Chemoresistance limits the therapeutic effect of cisplatin (DDP) on non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) function as important regulators in chemoresistance. This study aimed to explore the regulation of circRNA Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Alpha (circ_PIP5K1A) in DDP resistance. Methods The expression analysis of circ_PIP5K1A, micoRNA-493-5p (miR-493-5p) and Rho Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1) was conducted through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell sensitivity was determined using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell proliferation and cell viability were evaluated by colony formation assay and MTT assay, respectively. Cell cycle and apoptosis detection was performed via flow cytometry. Cell motility was examined by transwell migration or invasion assay. Dual-luciferase reporter assay was applied to confirm the target binding. ROCK1 protein level was assayed via Western blot. In vivo assay was carried out using xenograft model in mice. Results Circ_PIP5K1A level was abnormally increased in DDP-resistant NSCLC tissues and cells. Silencing circ_PIP5K1A reduced DDP resistance, proliferation, cell cycle progression and cell motility in DDP-resistant NSCLC cells. Circ_PIP5K1A directly interacted with miR-493-5p in NSCLC cells. The function of circ_PIP5K1A was dependent on the negative regulation of miR-493-5p. MiR-493-5p directly targeted ROCK1 and circ_PIP5K1A regulated the ROCK1 level via acting as a sponge of miR-493-5p. Overexpression of miR-493-5p inhibited chemoresistance and cancer progression by downregulating ROCK1 expression in DDP-resistant NSCLC cells. Circ_PIP5K1A regulated DDP sensitivity in vivo via the miR-493-5p/ROCK1 axis. Conclusion These findings suggested that circ_PIP5K1A upregulated the ROCK1 expression to promote DDP resistance and cancer progression in NSCLC by sponging miR-493-5p.

CALCR knockdown inhibits the development and progression of non-small-cell lung cancer

2021 ◽  
Author(s):  
Tao He ◽  
Feng Ling
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Expression Level ◽  
Cell Counting ◽  
Small Cell Lung

Abstract G protein-coupled receptors (GPCRs) have been reported to participant in the occurrence and development of a variety of human cancers. CALCR is one of the hundreds of GPCRs, but its expression level and functional importance have never been investigated in non-small-cell lung cancer (NSCLC). In the present study, the protein expression level of CALCR was detected by immunohistochemical staining and western blot analysis. The Celigo cell counting assay was used to assess cell proliferation. Both the wound healing assay and the transwell assay were performed to evaluate cell migration. Flow cytometric analysis was utilized to detect cell apoptosis and cell cycle. A mouse xenograft model was constructed to conduct the in vivo experiments. The results indicated that the CALCR expression was abundantly up-regulated in NSCLC and positively related to tumor infiltrate. Besides, CALCR knockdown could significantly suppress cell proliferation, migration, enhance apoptosis and arrest cell cycle. The in vivo study verified the inhibitory effects of CALCR knockdown on NSCLC tumorigenesis. The abovementioned results provided a reference for the treatment of NSCLC, that was, CALCR knockdown might be a considerable therapeutic strategy.

scholarly journals Knockdown of Immature Colon Carcinoma Transcript 1 Inhibits Proliferation and Promotes Apoptosis of Non–Small Cell Lung Cancer Cells

2016 ◽  
Vol 16 (5) ◽  
pp. 559-569 ◽  
Author(s):  
Yiling Wang ◽  
Jiantao He ◽  
Shenghui Zhang ◽  
Qingbo Yang ◽  
Bo Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Colon Carcinoma ◽  
Cancer Cell ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cell ◽  
Small Cell Lung

Non–small cell lung cancer, as the most frequent type lung cancer, has lower survival rate of 5 years, despite improvements in surgery and chemotherapy. Previous studies showed immature colon carcinoma transcript 1 is closely related to tumorigenesis of human cancer cells. In the present study, we found immature colon carcinoma transcript 1 was overexpressed in lung cancer tissues using Oncomine database mining, and the biological effect of immature colon carcinoma transcript 1 was investigated in non–small cell lung cancer cell lines 95D and A549. Lentivirus-mediated RNA interference was used to knock down immature colon carcinoma transcript 1 expression in 95D and A549 cells in vitro, and the knockdown efficiency was determined using quantitative real-time polymerase chain reaction and Western blot assay. Knockdown of immature colon carcinoma transcript 1 significantly suppressed non–small cell lung cancer cell proliferation and colony formation ability confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Flow cytometry was applied to measure cell cycle arrest, and the result showed the cell cycle arrested in G2/M phase in 95D cells and arrested in G0/G1 phase in A549 cells. Furthermore, we measured the levels of cell cycle–associated proteins by Western blot analysis and found immature colon carcinoma transcript 1 –mediated cell proliferation inhibition appeared due to downregulation of cell cycle activator cyclin D1 and upregulation of cell cycle inhibitor p21. In addition, immature colon carcinoma transcript 1 silencing significantly induced non–small cell lung cancer cell apoptosis by annexin V/7-amino-actinomycin D double-staining assay. All our data suggest that immature colon carcinoma transcript 1 may play an important role for non–small cell lung cancer cell proliferation and could be a potential molecular target for diagnosing and treating human non–small cell lung cancer.

scholarly journals MiR-421 Is Overexpressed and Promotes Cell Proliferation in Non-Small Cell Lung Cancer

2019 ◽  
Vol 29 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Xing Li ◽  
Shao-Hua Chen ◽  
Jin-Wu Zeng
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Tumor Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cell Counting ◽  
Small Cell Lung ◽  
Nsclc Patients

Background: Lung cancer is the main cause of cancer-­related deaths worldwide, and the overall 5-year survival rate of non-small cell lung cancer (NSCLC) remained low. ­MicroRNAs had been confirmed to be an important regulator in tumor progression, and they could serve as either tumor promoters or suppressors in NSCLC. Objectives: To identify the novel cancer-specific biomarkers for NSCLC patients, which may be useful to monitor tumor progression and improve NSCLC patients’ survival. Method: The expression profile of miR-421 was analyzed in NSCLC samples using public datasets, including The Cancer Genome Atlas and GSE102286. The expression level of miR-421 was detected by reverse transcription-polymerase chain reaction. Cell proliferation and cell cycle were detected by Cell Counting Kit assay, flow cytometry assay, respectively. Kyoto Encyclopedia of Genes and Genomes analysis were applied to determine the biological roles of miR-421, based on the online DAVID system. Statistical comparisons between groups of normalized data were performed using t test or Mann-Whitney U test according to the test condition. Results: In this study, we focused on exploring the roles of miR-421 in NSCLC prognosis and growth. The present study for the first time showed that miR-421 was overexpressed in NSCLC and associated with a shorter overall survival time of patients with NSCLC. Bioinformatics analysis revealed miR-421 was involved in transcription, cell cycle, and insulin signaling pathway regulation. Furthermore, a gain of function assay showed that overexpression of miR-421 could promote NSCLC cell proliferation and cell cycle progression. Conclusions: Our findings suggest that miR-421 might be a promising prognostic and therapeutic target for NSCLC.

scholarly journals Circ_0018534 Promotes Non-Small Cell Lung Cancer Progression by Upregulating BTBD7 via Sponging miR-153-3p

2021 ◽  
Author(s):  
Haoran Bai ◽  
Lihua Zhu ◽  
Hegen Li ◽  
Lei Zhou
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Nsclc Patient ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background: Non-small cell lung cancer (NSCLC) is the most common malignant tumor in lung. In this study, we aimed to explore the role and underlying mechanism of circular RNA 0018534 (circ_0018534) in NSCLC progression.Methods: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of circ_0018534, microRNA-153-3p (miR-153-3p) and BTB/POZ domain-containing protein 7 (BTBD7) in NSCLC tissues and cells. Protein expression was measured by western blot analysis. The morphological features of obtained NSCLC patient tissues were observed by haematoxylin and eosin staining assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, and transwell migration and invasion assays were used to examine cell viability, proliferation, apoptosis, migration and invasion, respectively. Bioinformatics analysis and dual-luciferase reporter assay were carried out to determine the interaction among circ_0018534, miR-153-3p and BTBD7. Furthermore, lentivector for short hairpin RNA against circ_0018534 (sh-circ_0018534) was used to decrease circ_0018534 expression in an animal tumor model.Results: Circ_0018534 and BTBD7 expression were significantly increased, whereas miR-153-3p expression was decreased in NSCLC tissues and cells. Circ_0018534 downregulation markedly alleviated cell proliferation, migration, invasion, and elevated cell apoptosis in NSCLC cells in vitro. MiR-153-3p inhibitors partially reversed the effects of circ_0018534 knockdown on cell proliferation, migration, invasion and apoptosis in NSCLC. Moreover, miR-153-3p could directly target BTBD7, and circ_0018534 promoted BTBD7 expression by targeting miR-153-3p. Besides, BTBD7 overexpression attenuated miR-153-3p mimics-mediated effects on NSCLC cell progression. Furthermore, circ_0018534 deletion suppressed NSCLC tumor growth in vivo.Conclusion: Our results demonstrated that circ_0018534 might contribute to the progression of NSCLC by miR-153-3p/BTBD7 axis, providing a potential target for the treatment of NSCLC.

scholarly journals tRF-Leu-CAG promotes cell proliferation and cell cycle in non-small cell lung cancer

2017 ◽  
Vol 90 (5) ◽  
pp. 730-738 ◽  
Author(s):  
Yang Shao ◽  
Qiangling Sun ◽  
Xiaomin Liu ◽  
Ping Wang ◽  
Renqi Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung
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