scholarly journals Identification of Differential Genes by Microarray and COL6A1 Induced the Bone Metastasis of Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Nan Li ◽  
Xiaohui Cao ◽  
Wei Li ◽  
Yunfang Li ◽  
Zongmao Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Western Blot ◽  
Pathway Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Tissue ◽  
Alizarin Red ◽  
Tissue Samples ◽  
Adhesion Ability

Abstract Background: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide with bone metastasis as the most prevalent events in advanced cancer patients. However, its pathogenesis has not been clearly described. Methods: In the present study, differentially expressed genes (DEGs) were filtered through gene expression microarray between NSCLC tissue samples with or without bone metastasis. Subsequently, collagen family collagen 6A1 (COL6A1) was chosen as the target gene through Ingenuity Pathway Analysis and qRT-PCR validation of the 8 Top genes. And we evaluated the osteogenic capacity of HOB and hES-MP 002.5 cells through RT-qPCR, Western blot, Alizarin Red Staining and ALP staining.Results: A total of 364 DEGs including 140 up-regulated genes and 224 down-regulated genes were identified in NSCLC tissues with bone metastasis. GO analysis indicated that the upregulated and downregulated genes were mainly enriched in cellular process, metabolic process and biological regulation. KEGG pathway analysis revealed that the upregulated genes were mainly concentrated in cysteine and methionine metabolism, oxidative phosphorylation, and ribosome; the downregulated genes were mainly concentrated in the transcriptional misregulation in cancer, ribosome, and mitophagy-animal. Besides, the results of RT-qPCR, western blot and immunohistochemistry proved that COL6A1 was highly expressed in NSCLC tissue samples with bone metastasis. And we revealed that HOB and hES-MP 002.5 cells have osteogenic capacity through RT-qPCR, Western blot, Alizarin Red Staining and ALP staining . Moreover, the results of cell adhesion assay also proved that high expression of COL6A1 in HARA-B cells can induce its adhesion ability on osteoblasts, and low expression of COL6A1 in HARA-B cells can reduce its adhesion ability on osteoblasts. Conclusions: Therefore, our data revealed that the COL6A1 might represent a diagnostic marker or therapeutic target for bone metastasis in NSCLC.

scholarly journals Correlation of exosomal microRNA clusters with bone metastasis in non-small cell lung cancer

2020 ◽  
Author(s):  
Xiao-Rong Yang ◽  
Can Pi ◽  
Ruoying Yu ◽  
Xiao-Jun Fan ◽  
Xiao-Xiao Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Pathway Analysis ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients

Abstract20–40% of lung cancer patients develop bone metastasis (BM) with significantly decreased overall survival. Currently, BM is mainly diagnosed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) when symptom develops. Novel biomarkers with higher prediction value of BM are needed. Plasma-derived exosomal microRNAs had been isolated and sequenced of total 30 non-small cell lung cancer (NSCLC) patients including 16 with bone metastasis and 14 without bone metastasis. Hierarchical clustering based on the total miRNA profile can clearly separate cancer patients and healthy individuals (H), but not patients with (BM +) or without (BM−) BM. Weight Co-expression network of miRNAs (WGCNA) analyses identified three consensus clusters (A, B, C) of highly correlated miRNAs, among which cluster B (144 miRNAs) showed significantly differential expression in lung cancer patients, especially in BM + group. Pathway analysis of cluster B miRNAs revealed enrichment in metabolic pathways that may involve in preconditioning of the metastatic niche. Three differentially expressed miRNAs between BM + and BM− patients within cluster B were identified as miR-574-5p, a suppressor of Wnt/β-catenin pathway, was down-regulated, while miR-328-3p and miR-423-3p, two activators of the same pathway, were up-regulated in BM + patients. Cluster A miRNAs (n = 49) also showed trend of upregulation in BM + patients. Interestingly, pathway analysis indicated that 43 of them are associated with chromosome14, which has been suggested to promote epithelial-mesenchymal transition (EMT) and bone metastasis.

scholarly journals LncRNA MIR210HG Facilitates Non-Small Cell Lung Cancer Progression Through Directly Regulation of miR-874/STAT3 Axis

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582091805
Author(s):  
Liang Bu ◽  
Libin Zhang ◽  
Mei Tian ◽  
Zhoubin Zheng ◽  
Huijie Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Nsclc Tissue ◽  
Tissue Samples ◽  
Cell Progression

Background: Long noncoding RNAs are involved in the progression of multiple cancers. However, the expression and mechanism of microRNA (miR)210HG in non-small cell lung cancer (NSCLC) remain unclear. Methods: The levels of miR210HG and miR-874 were measured by quantitative real-time polymerase chain reaction in NSCLC tissue samples and cells. Non-small cell lung cancer cell proliferation, migration, and invasion were measured by Cell Counting Kit-8 and transwell assays. Luciferase analysis confirmed the interaction between miR210HG and miR-874. Results: Here, our data showed that miR210HG was overexpressed in NSCLC tissue samples and cells. In vitro functional assays showed that silencing miR210HG blocked NSCLC cell proliferation, migration, and invasion while promoting NSCLC cell radiosensitivity and chemoresistance. Mechanistically, miR-874 was directly regulated by miR210HG. Furthermore, miR-874 expression was reduced in NSCLC tissues and cells. The miR-874 mimic could mitigate the promoting effect of miR210HG on NSCLC cell progression. The data also showed that miR210HG promoted NSCLC cell progression through miR-181a expression by targeting STAT3. Conclusions: Our observations suggest that miR210HG is associated with NSCLC cell progression by regulating the miR-874/STAT3 axis.

Curcumin increases crizotinib sensitivity through the inactivation of autophagy via epigenetic modulation of the miR-142-5p/Ulk1 axis in non-small cell lung cancer

2021 ◽  
pp. 1-11
Author(s):  
Yu-Zheng He ◽  
Shan-Ling Yu ◽  
Xiao-Ning Li ◽  
Xian-Hua Bai ◽  
Hai-Tao Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Critical Factor ◽  
Underlying Mechanism ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Tissue ◽  
Tissue Samples ◽  
H460 Cells

Drug resistance is a critical factor responsible for the recurrence of non-small cell lung cancer (NSCLC). Previous studies suggest that curcumin acts as a chemosensitizer and radiosensitizer in human malignancies, but the underlying mechanism remains elusive. In the present study, we explored how curcumin regulates the expression of miR-142-5p and sensitizes NSCLC cells to crizotinib. We found that miR-142-5p is significantly downregulated in NSCLC tissue samples and cell lines. Curcumin could increase crizotinib cytotoxicity by epigenetically restoring the expression of miR-142-5p. Furthermore, curcumin treatment suppressed the expression of DNA methylation-related enzymes, including DNMT1, DNMT3A, and DNMT3B, in NSCLC cells. In addition, the upregulation of miR-142-5p expression increased crizotinib cytotoxicity and induced apoptosis in tumor cells in a similar manner to that of curcumin. Strikingly, miR-142-5p overexpression suppressed crizotinib-induced autophagy in A549 and H460 cells. Mechanistically, miR-142-5p inhibited autophagy in lung cancer cells by targeting Ulk1. Overexpression of Ulk1 abrogated the miR-142-5p-induced elevation of crizotinib cytotoxicity in A549 and H460 cells. Collectively, our findings demonstrate that curcumin sensitizes NSCLC cells to crizotinib by inactivating autophagy through the regulation of miR-142-5p and its target Ulk1.

scholarly journals Bone metastasis unique plasma exosomal microRNA signature in non-small cell lung cancer

2020 ◽  
Author(s):  
Can Pi ◽  
Xiaorong Yang ◽  
Ruoying Yu ◽  
Xiaojun Fan ◽  
Xiaoxiao Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Differential Expression ◽  
Pathway Analysis ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

Abstract Background 20–40% of lung cancer patients develop bone metastasis (BM) with significantly decreased overall survival. Currently, BM is mainly diagnosed by CT scan or MRI when symptom develops. Novel biomarkers with higher prediction value of BM are needed. Methods Prospective analysis was undertaken on non-small cell lung cancer (NSCLC) patients with (BM+) and without BM (BM-). Plasma exosomal RNA was isolated and sequenced from peripheral blood of patients. Differential expression analysis and weighted gene co-expression networks analysis (WGCNA) of mi-RNA sequencing data were performed between two groups. Results Hierarchical clustering based on the total miRNA profile can clearly separate cancer patients and healthy individuals (H), but not patients BM + or BM-. WGCNA identified three consensus clusters (A, B, C) of highly correlated miRNAs, among which cluster B (144 miRNAs) showed significantly differential expression in lung cancer patients, especially in BM + group. Three differentially expressed miRNAs between BM + and BM- patients within cluster B were identified as miR-574-5p, a suppressor of Wnt/β-catenin pathway, was down-regulated, while miR-328-3p and miR-423-3p, two activators of the same pathway, were up-regulated in BM + patients. Pathway analysis of cluster B miRNAs revealed enrichment in metabolic pathways that may involve in preconditioning of the metastatic niche. Cluster A miRNAs (n = 49) also showed trend of upregulation in BM + patients. Interestingly, pathway analysis indicated that 43 of them are associated with chromosome14, which has been suggested to promote EMT and bone metastasis. Conclusion These data indicated that a cluster of mi-RNAs showed significantly differential expression in BM + group, including miR-574-5p, miR-328-3p and miR-423-3p.

scholarly journals Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Jianjiao Ni ◽  
Xiaofei Zhang ◽  
Juan Li ◽  
Zhiqin Zheng ◽  
Junhua Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Osteoclast Differentiation ◽  
Small Cell ◽  
Signalling Pathway ◽  
Small Cell Lung

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

scholarly journals Knockdown of lncRNA X inactive specific transcript (XIST) radiosensitizes non-small cell lung cancer (NSCLC) cells through regulation of miR-16-5p/WEE1 G2 checkpoint kinase (WEE1) axis

2021 ◽  
Vol 35 ◽  
pp. 205873842096608
Author(s):  
Ran Du ◽  
Feng Jiang ◽  
Yanhua Yin ◽  
Jinfen Xu ◽  
Xia Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Western Blot ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Luciferase Reporter Gene ◽  
G2 Checkpoint ◽  
Qrt Pcr ◽  
Specific Transcript

Long non-coding RNA (lncRNA) X inactive specific transcript (XIST) is reported to play an oncogenic role in non-small cell lung cancer (NSCLC). However, the role of XIST in regulating the radiosensitivity of NSCLC cells remains unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expressions of XIST and miR-16-5p in NSCLC in tissues and cells, and Western blot was used to assess the expression of WEE1 G2 checkpoint kinase (WEE1). Cell counting kit-8 (CCK-8), colony formation and flow cytometry assays were used to determine cell viability and apoptosis after NSCLC cells were exposed to different doses of X-rays. The interaction between XIST and miR-16-5p was confirmed by StarBase database, qRT-PCR and dual-luciferase reporter gene assays. TargetScan database was used to predict WEE1 as a target of miR-16-5p, and their targeting relationship was further validated by Western blot, qRT-PCR and dual-luciferase reporter gene assays. XIST was highly expressed in both NSCLC tissue and cell lines, and knockdown of XIST repressed NSCLC cell viability and cell survival, and facilitated apoptosis under the irradiation. MiR-16-5p was a target of XIST, and rescue experiments demonstrated that miR-16-5p inhibitors could reverse the role of XIST knockdown on radiosensitivity in NSCLC cells. WEE1 was validated as a target gene of miR-16-5p, and WEE1 could be negatively regulated by XIST. XIST promotes the radioresistance of NSCLC cells by regulating the expressions of miR-16-5p and WEE1, which can be a novel target for NSCLC therapy.

scholarly journals Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway

2018 ◽  
Vol 51 (5) ◽  
pp. 2136-2147 ◽  
Author(s):  
Haiting Gu ◽  
Junfeng Chen ◽  
Yukang Song ◽  
Haiyan Shao
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Non Coding Rna

Background/Aims: Long non-coding RNAs (lncRNAs) play vital roles in carcinogenesis as oncogenes or tumor suppressor genes. This study explored the biological function of lncRNA gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in human non-small cell lung cancer (NSCLC). Methods: GAPLINC expression in NSCLC specimens and cell lines was detected by qRT-PCR and Western blot. The effect of GAPLINC on cell proliferation was investigated using CCK8-assay, colony formation assay, and xenograft model. The effects of GAPLINC on apoptosis and cell cycle were determined using flow cytometry. The mechanism of GAPLINC involved in NSCLC was explored using Western blot, luciferase reporter assay, and RNA fluorescence in situ hybridization. Results: We found that GAPLINC expression was up-regulated in NSCLC tissues and cell lines. Overexpression of GAPLINC was associated with poor prognosis in patients with NSCLC. Silencing of GAPLINC significantly inhibited cell proliferation, promoted apoptosis, and induced cell cycle arrest in the G0/G1 phase. Results from xenograft transplantation showed that GAPLINC silencing inhibited the tumor growth in vivo. Interestingly, GAPLINC silencing decreased the expression of eukaryotic elongation factor-2 kinase (eEF2K) protein both in vivo and in vitro. Bioinformatic analysis and luciferase reporter confirmed that miR-661 targeted GAPLINC and eEF2K 3’-UTR and was negatively correlated with the expression of GAPLINC and eEF2K. Conclusion: Our findings indicate that GAPLINC promotes NSCLC tumorigenesis by regulating miR-661/eEF2K cascade and provide new insights for the pathogenesis underlying NSCLC and potential targets for therapeutic strategy.

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