scholarly journals lncRNA Gm15290 promotes cell proliferation and invasion in lung cancer through directly interacting with and suppressing the tumor suppressor miR-615-5p

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Yu Dong ◽  
Xiaoying Huo ◽  
Ruiying Sun ◽  
Zhiyan Liu ◽  
Miaoyi Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Target Genes ◽  
A549 Cells ◽  
Normal Lung ◽  
Nsclc Patients ◽  
Proliferation And Invasion

Long non-coding RNAs (lncRNAs) have been involved in occurrence and progression of multiple cancers. In the present study, we investigated the role of lncRNA Gm15290 in the proliferation and invasion of non-small cell lung cancer (NSCLC) cells. First, we found that lncRNA Gm15290 was markedly up-regulated in tumor tissues from NSCLC patients and NSCLC cell lines, compared with adjacent normal tissues and normal lung cell line HBE respectively. Then, different concentrations of pcDNA-Gm15290 expression vector and Gm15290 siRNA were respectively transfected into A549 NSCLC cells. Our results showed that overexpression of Gm15290 significantly increased the proliferation and invasion of A549 cells and suppressed cell apoptosis. Knockdown of Gm15290 suppressed A549 cell proliferation and invasion and promoted cell apoptosis. Subsequently, we explored the underlying mechanism through which Gm15290 promoted cell proliferation and invasion. The output of RNA hybrid bioinformatic tool revealed that Gm15290 potentially interacted with tumor suppressor miR-615-5p which displayed an opposite expression pattern in the cell lines and a strong negative correlation with the levels of Gm15290 in NSCLC patients (r2 = 0.9677, P<0.0001). The results of RNA pull-down assays confirmed that Gm15290 directly bound with miR-615-5p. Gm15290 negatively regulated the expression of miR-615-5p and increased the protein levels of miR-615-5p target genes, including IGF2, AKT2, and SHMT2. Moreover, miR-615-5p mimic could antagonize the promoting effect of Gm15290 on cell proliferation and invasion.

scholarly journals Long non-coding RNA DUXAP8 regulates the cell proliferation and invasion of non-small-cell lung cancer

2019 ◽  
Vol 14 (1) ◽  
pp. 201-207
Author(s):  
Si-Jia Yang ◽  
Jia-Lu Weng ◽  
Bin Wei ◽  
Xue-Kui Du
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Proliferation And Invasion

AbstractTo investigate how long non-coding RNAs DUXAP8 (LncRNA DUXAP8) influence the cell proliferation and invasion of non-small-cell lung cancer (NSCLC), we detected the expression levels of LncRNA DUXAP8 in lung cancer (LC) tissues, 4 LC-related cell lines (A549, SPC-A1, SK-MES-1 and NCI-H1299) and normal lung tissues via quantitative real-time PCR (qRT-PCR). Compared with normal lung tissue, LncRNA DUXAP8 was significantly up-regulated in NSCLC, especially in stage III / IV and diameter ≥ 3cm of lung cancer. Among 4 lung cancer cell lines, LncRNA DUXAP8 in A549 cells was the highest (P<0.001). Construction of LncRNA DUXAP8 overexpression and LncRNA DUXAP8 knockout in A549 cell lines was further performed and subsequently injected into nude mice to build an in vivo tumor xenograft model. The results indicated that LncRNA DUXAP8 overexpression significantly promoted the A549 cells’ proliferation, enhanced invasion and induced tumor growth. Conversely, LncRNA DUXAP8 knockout significantly suppressed A549 cells’ proliferation, weakened invasion and inhibited tumor growth. Taken together, our results imply that LncRNA DUXAP8 is a potential regulatory molecular marker in non-small-cell lung cancer.

scholarly journals LncRNA PCAT1 Interacts with DKC1 to Regulate Proliferation, Invasion and Apoptosis in NSCLC Cells via the VEGF/AKT/Bcl2/Caspase9 Pathway

2021 ◽  
Vol 30 ◽  
pp. 096368972098607
Author(s):  
Shi-Yuan Liu ◽  
Zhi-Yu Zhao ◽  
Zhe Qiao ◽  
Shao-Min Li ◽  
Wei-Ning Zhang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Cell Apoptosis ◽  
Rna Binding ◽  
A549 Cells ◽  
Nonsmall Cell Lung Cancer ◽  
Nsclc Cell ◽  
Loss Of Function ◽  
Proliferation And Invasion

Long noncoding RNAs (lncRNAs) are increasingly recognized as indispensable components of the regulatory network in the progression of various cancers, including nonsmall cell lung cancer (NSCLC). The lncRNA prostate cancer associated transcript 1 (PCAT1) has been involved in tumorigenesis of multiple malignant solid tumors, but it is largely unknown that what is the role of lncRNA-PCAT1 and how it functions in the progression of lung cancer. Herein, we observed that lncRNA PCAT1 expression was upregulated in both human NSCLC tissues and cell lines, which was determined by qualitative polymerase chain reaction analysis. Then, gain-and loss-of-function manipulations were performed in A549 cells by transfection with a specific short interfering RNA against PCAT1 or a pcDNA-PCAT1 expression vector. The results showed that PCAT1 not only promoted NSCLC cell proliferation and invasion but also inhibited cell apoptosis. Bioinformatics and expression correlation analyses revealed that there was a potential interaction between PCAT1 and the dyskerin pseudouridine synthase 1 (DKC1) protein, an RNA-binding protein. Then, RNA pull-down assays with biotinylated probes and transcripts both confirmed that PCAT1 directly bounds with DKC1 that could also promote NSCLC cell proliferation and invasion and inhibit cell apoptosis. Moreover, the effects of PCAT1 and DKC1 on NSCLC functions are synergistic. Furthermore, PCAT1 and DKC1 activated the vascular endothelial growth factor (VEGF)/protein kinase B (AKT)/Bcl-2/caspase9 pathway in NSCLC cells, and inhibition of epidermal growth factor receptor, AKT, or Bcl-2 could eliminate the effect of PCAT1/DKC1 co-overexpression on NSCLC cell behaviors. In conclusion, lncRNA PCAT1 interacts with DKC1 to regulate proliferation, invasion, and apoptosis in NSCLC cells via the VEGF/AKT/Bcl-2/caspase9 pathway.

scholarly journals miR-27a-3p Functions as a Tumor Suppressor and Regulates Non-Small Cell Lung Cancer Cell Proliferation via Targeting HOXB8

2019 ◽  
Vol 18 ◽  
pp. 153303381986197 ◽  
Author(s):  
Xiaohong Yan ◽  
Hui Yu ◽  
Yao Liu ◽  
Jie Hou ◽  
Qiao Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Normal Cell ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Normal Cell Line

MicroRNA-27a-3p has been implicated to play crucial roles in human cancers. However, the biological role and underlying mechanisms of microRNA-27a-3p in regulating nonsmall lung cancer remain unclear. MicroRNA-27a-3p expression levels in non-small lung cancer cell lines were detected by quantitative real-time polymerase chain reaction, using a normal cell line as control. The effects of microRNA-27a-3p on cell proliferation and apoptosis were analyzed by Cell Counting Kit-8 assay and flow cytometry assay. Luciferase activity reporter assay and Western blot were conducted to validate the potential targets of miR27a-3p after preliminary screening by TargetScan. Effect of microRNA-27a-3p or homeobox B8 on the overall survival of patients with non-small lung cancer was analyzed at Kaplan-Meier Plotter website. MicroRNA-27a-3p expression levels were significantly reduced in non-small lung cancer cell lines compared with normal cell line. Overexpression of microRNA-27a-3p inhibits non-small lung cancer cell proliferation but promotes cell apoptosis. Homeobox B8 was further validated as a functional target of microRNA-27a-3p. Collectively, our results indicated that microRNA-27a-3p acts as a tumor suppressor in non-small lung cancer via targeting homeobox B8.

FOXD3-AS1 suppresses the progression of non-small cell lung cancer by regulating miR-150/SRCIN1axis

2020 ◽  
Vol 29 (3) ◽  
pp. 417-427 ◽  
Author(s):  
Tao Ji ◽  
Yanan Zhang ◽  
Zheng Wang ◽  
Zuoxu Hou ◽  
Xuhui Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Gene Assay ◽  
Proliferation And Invasion

BACKGROUND: Long non-coding RNA (lncNRA) forkhead box D3 antisense RNA 1 (FOXD3-AS1) has been proved to promote or suppress the occurrence and development of multiple types of human tumors. However, the function and mechanism of FOXD3-AS1 in non-small cell lung cancer (NSCLC) are scarcely understood. METHODS: qRT-PCR was used for detecting FOXD3-AS1, miR-150 and SRC kinase signaling inhibitor 1 (SRCIN1) mRNA expression in NSCLC tissues, and the relationship between pathological characteristics of NSCLC patients and FOXD3-AS1 expression level was analyzed. With human NSCLC cell lines H1299 and A549 as cell models, CCK-8 and BrdU assays were employed for detecting cancer cell proliferation, and Transwell assay was employed for detecting cell invasion ability. Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used for the verification of the targeting relationshipe between FOXD3-AS1 and miR-150, and Western blot was employed for detecting SRCIN1 protein expression. RESULTS: FOXD3-AS1 expression was significantly reduced in NSCLC tissues and cell lines, and low expression of FOXD3-AS1 was closely related to positive lymph node metastasis and relatively high tumor grade. FOXD3-AS1 over-expression inhibited the proliferation and invasion of H1299 cell lines, while its knockdown promoted the proliferation and invasion of A549 cells. Additionally, it was confirmed that FOXD3-AS1 suppressed the expression of miR-150 by targeting it, and up-regulated the expression of SRCIN1. CONCLUSIONS: FOXD3-AS1 indirectly enhances the expression of SRCIN1 by targeting miR-150, thereby inhibiting NSCLC progression.

scholarly journals TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ke Ren ◽  
Jinghui Sun ◽  
Lingling Liu ◽  
Yuping Yang ◽  
Honghui Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Qrt Pcr ◽  
Proliferation And Invasion

Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. We found lncRNA GHRLOS was decreased in NSCLC cell lines and tissues which correlated with poor prognosis of NSCLC patients. However, the role and underlying mechanisms of lncRNA GHRLOS in NSCLC progression remains elusive. The expression of lncRNA GHRLOS was examined in NSCLC cell lines and biopsy specimens of patients with NSCLC by quantitative real time polymerase chain reaction (qRT-PCR). The effects of GHRLOS on proliferation, invasion and apoptosis of NSCLC cells were determined by both in vitro and in vivo experiments. The interaction between GHRLOS and TP53 was determined by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) combined with qRT-PCR analysis. RNA immunoprecipitation (RIP) was conducted to validate the binding between GHRLOS and microRNA-346 (miR-346). Dual-luciferase reporter assays were also carried out to reveal the interaction between miR-346 and the 3’ untranslated region (3’UTR) of adenomatous polyposis coli (APC) mRNA.Our data demonstrated that overexpression of lncRNA GHRLOS suppressed cancer cell proliferation and invasion as well as promoted cell apoptosis by regulating the expression of CDK2, PCNA, E-cadherin, N-cadherin, Bax, and Bcl-2 in NSCLC cells. Moreover, lncRNA GHRLOS was upregulated by the binding of TP53 to the GHRLOS promoter. The binding target of lncRNA GHRLOS was identified to be miR-346. Impressively, overexpression of miR-346 promoted cell proliferation and invasion, as well as inhibited cell apoptosis, however, these effects can be blocked by overexpression of lncRNA GHRLOS both in vitro and in vivo. In summary, this study reveals lncRNA GHRLOS, upregulated by TP53, acts as a molecule sponge of miR-346 to cooperatively modulates expression of APC, a miR-346 target, and potentially inhibits NSCLC progression via TP53/lncRNA GHRLOS/miR-346/APC axis, which represents a novel pathway that could be useful in targeted therapy against NSCLC.

scholarly journals m6A demethylase ALKBH5 promotes tumor cell proliferation by destabilizing IGF2BPs target genes and worsens the prognosis of patients with non-small cell lung cancer

2021 ◽  
Author(s):  
Kazuo Tsuchiya ◽  
Katsuhiro Yoshimura ◽  
Yuji Iwashita ◽  
Yusuke Inoue ◽  
Tsutomu Ohta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Target Genes ◽  
Small Cell ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Proliferation Ability

Background: The modification of N6-methyladenosine (m6A) in RNA and its eraser ALKBH5, an m6A demethylase, play important roles across various steps of human carcinogenesis. However, the involvement of ALKBH5 in non-small cell lung cancer (NSCLC) development remains to be completely elucidated. Methods: The current study investigated the involvement of ALKBH5 in NSCLC development using immunostaining of clinical NSCLC specimens as well as cancer-related cellular functions (cell proliferation, migration ability, cell cycle, and apoptosis) in ALKBH5-knockdown lung cancer cell lines. Moreover, a microarray was utilized to comprehensively analyze mRNA and m6A in ALKBH5-knockdown cells. m6A target genes were identified using the methylated RNA immunoprecipitation (MeRIP) assay with m6A antibody. Furthermore, mRNA stability and protein expression owing to m6A modification (the target genes) were examined. Results: Clinicopathological analysis revealed that increased ALKBH5 expression was an independent prognostic factor associated with unfavorable overall survival in NSCLC (hazard ratios, 1.468; 95% confidence interval, 1.039—2.073). In vitro study revealed that ALKBH5 knockdown suppressed cell proliferation ability of PC9 and A549 cells as well as promoted G1 arrest and increased the number of apoptotic cells. Furthermore, ALKBH5 overexpression increased the cell proliferation ability of the immortalized cell lines BEAS2B and HEK293. Comprehensive analysis of microarray and MeRIP quantitative-polymerase chain reaction revealed that 3′ untranslated regions (3′ UTRs) of CDKN1A, TIMP3, E2F1, and CCNG2 mRNA were potential targets of ALKBH5. Depending on the lung cancer cell lines, increased expression of CDKN1A or TIMP3 and decreased cell proliferation were observed by ALKBH5 knockdown. These alterations were offset by a double knockdown of both ALKBH5 and one of the IGF2BPs. The decline of mRNAs was, at least partly, owing to the destabilization of these mRNAs by one of the IGF2BPs. Conclusions: Upregulation of ALKBH5 in NSCLC reduces m6A modifications on the 3′ UTR of specific genes. Loss of m6A causes a decrease in opportunity for recognition by IGF2BPs and destabilizes the target transcript, such as CDKN1A (p21) and TIMP3. Downregulation of CDKN1A (p21) and TIMP3 induces cell cycle alteration and inhibits apoptosis. The ALKBH5—IGF2BPs axis promotes cell proliferation and tumorigenicity, which in turn causes the unfavorable prognosis of NSCLC.

scholarly journals Downregulated Long Noncoding RNA PART1 Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer

2019 ◽  
Vol 18 ◽  
pp. 153303381984663 ◽  
Author(s):  
Xin Hu ◽  
Hefei Feng ◽  
Huaxing Huang ◽  
Wei Gu ◽  
Qiuyu Fang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Ribonucleic Acid ◽  
Cell Apoptosis ◽  
Bladder Cancer Cell ◽  
Proliferation And Apoptosis ◽  
Proliferation And Invasion

Objective: In this study, we aimed to clarify the effects of long noncoding ribonucleic acid prostrate androgen-regulated transcript-1 on bladder cancer cell proliferation and apoptosis. Methods: Microarrays were implemented to investigate the long noncoding ribonucleic acid expression profiles in bladder cancer tissue (N = 9) and in noncancer bladder tissue (N = 5). Relative prostrate androgen-regulated transcript-1 expression levels in tissue samples or cell lines were detected by real-time quantitative reverse transcription-polymerase chain reaction. Prostrate androgen-regulated transcript-1 expression was enhanced by the transfection of pcDNA3.1-prostrate androgen-regulated transcript-1 and downregulated by the infection with pcMV-sh prostrate androgen-regulated transcript-1. Additionally, cell proliferation and apoptosis were measured by the cell counting kit-8 assay and flow cytometry, respectively. Cell invasion was determined by a Transwell assay. Results: Prostrate androgen-regulated transcript-1 expression was upregulated in bladder cancer tissues compared to adjacent nontumor tissues. Furthermore, prostrate androgen-regulated transcript-1 levels were successfully upregulated by pcDNA3.1-prostrate androgen-regulated transcript-1 and depleted by pCMV-sh prostrate androgen-regulated transcript-1 in bladder cancer cell lines (5637, T24). Enhanced prostrate androgen-regulated transcript-1 expression promoted cell proliferation and invasion and inhibited cell apoptosis. However, knockdown of prostrate androgen-regulated transcript-1 expression inhibited cell proliferation and invasion and induced cell apoptosis. Conclusion: In summary, these data suggest that the knockdown of prostrate androgen-regulated transcript-1 represents a tumor suppressor player in bladder cancer and contributes to the inhibition of tumor proliferation, the promotion of cell apoptosis, and the suppression of cell invasion. Prostrate androgen-regulated transcript-1 may function as a new prognostic biomarker and as a feasible therapeutic target for patients with bladder cancer.

Targeting Na+/K+-ATPase in non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18144-18144
Author(s):  
B. Nilsson ◽  
T. Mijatovic ◽  
A. Mathieu ◽  
I. Roland ◽  
E. Van Quaquebeke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Migration And Proliferation

18144 Background: Non-small cell lung cancer patients that present with grade IIIB or stage IV disease have a median survival of 5–7 months if left untreated. With modern chemotherapy overall survival may be 11–12 months, but still no patients are cured. We have investigated the impact of modulation of the a-1 subunit of Na+/K+-ATPase in NSCLC. Methods: Cancer tissue from 59 patients with NSCLC (30 adenocarcinomas and 29 squamous cell cancers) and 25 normal lung samples as well as four human NSCLC cell lines (A549, Cal-12T, NCI-H727, A427) were assessed with regard to expression of the a-1 subunit of Na+/K+-ATPase (sodium pump) by use of immunohistochemistry. In addition, A549 cells were transfected with specific a-1 siRNA for study of a-1 subunit expression and of cell proliferation and migration. Protein expression was analyzed by Western blotting. Cell proliferation was assessed by MTT and cell migration by video microscopy. Cell lines were exposed to varying concentrations of ouabain, digoxin, digitoxin and UNBS1450, a novel cardenolide targeting the a-1 subunit of Na+/K+-ATPase for study of proliferation, migration, and inhibition of the target. Results: Expression of the a-1 subunit of Na+/K+- ATPase was elevated in almost half of the tissue samples from patients with NSCLC compared to normal controls. The a-1 subunit was also overexpressed in A549, Cal-12T and NCI-H727 cells. Transfection of A549 cells with siRNA resulted in markedly decreased expression of the a- 1 subunit and also to reduced migration and proliferation of such cells. UNBS1450 at 10 and 100 nM for 72 hours reduced A549 cell migration and proliferation similar to that observed with anti- a-1 siRNA. Digoxin had no activity at these concentrations. Conclusions: Inhibition of the a-1 subunit of Na+/K+-ATPase is associated with significant decrease of cell migration and proliferation and has potential as a therapeutic strategy in NSCLC. No significant financial relationships to disclose.

Dual inhibition of aromatase and epidermal growth factor receptor in non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22189-e22189
Author(s):  
A. Koutras ◽  
I. Kritikou ◽  
E. Giannopoulou ◽  
K. Dimitropoulos ◽  
H. Kalofonos
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Lines ◽  
A549 Cells ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Dual Inhibition

e22189 Background: Recent evidence suggests that estrogen signaling is important in the progression of cancers expressing estrogen receptors (ERs) and may also be involved in the pathogenesis of non-small cell lung cancer (NSCLC). Aromatase is an enzyme complex that catalyses the final step in estrogen synthesis and is present in several tissues, including the lung. In view of a possible functional interaction between the ER and the epidermal growth factor receptor (EGFR) pathways in NSCLC, we investigated the dual inhibition of aromatase and EGFR in NSCLC cell lines. Methods: In the current study we used exemestane, an irreversible steroidal aromatase inactivator, and erlotinib, an EGFR tyrosine kinase inhibitor. The in vitroexperiments were performed using H23 and A549, two NSCLC cell lines with low and high levels of aromatase, respectively. Cell proliferation was measured by MTT assay. Metalloproteinase (MMP) levels were detected by zymography and cell migration was determined by boyden chamber assay. EGFR protein levels detection was performed by immunofluorescense assay. Results: Exemestane and erlotinib inhibited H23 and A549 cell proliferation either alone or in combination, 48 hours after their application. However, the combination of exemestane and erlotinib was more effective than each agent alone, in H23 cells. Furthermore, exemestane decreased MMP-2 and MMP- 9 levels in H23 cells, whereas erlotinib did not. The combination of exemestane and erlotinib had the same effect on MMPs, as exemestane alone. The effect on cell migration was in line with the results in MMPs levels. In A549 cells, no changes in MMPs levels or cell migration were demonstrated. In addition, exemestane altered the location of EGFR protein in H23 cells, but not in A549 cells. Conclusions: Our findings suggest an antiproliferative effect of exemestane and erlotinib in both cell lines, as well as synergy for the combination in H23 cells. The activity of the combination in these cells with low levels of aromatase might involve an additional effect of exemestane on EGFR protein location. Erlotinib did not enhance the effect of exemestane on MMPs secretion and migration in H23 cells. No significant financial relationships to disclose.

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