scholarly journals Computational Prediction of Probable Single Nucleotide Polymorphism-Cancer Relationships

2020 ◽  
Vol 19 ◽  
pp. 117693512094221
Author(s):  
Shahab Bakhtiari ◽  
Sadegh Sulaimany ◽  
Mehrdad Talebi ◽  
Kabmiz Kalhor
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Link Prediction ◽  
Molecular Mechanisms ◽  
Preferential Attachment ◽  
Small Cell ◽  
Bipartite Network ◽  
Small Cell Lung ◽  
Single Nucleotide

Genetic variations such as single nucleotide polymorphisms (SNPs) can cause susceptibility to cancer. Although thousands of genetic variants have been identified to be associated with different cancers, the molecular mechanisms of cancer remain unknown. There is not a particular dataset of relationships between cancer and SNPs, as a bipartite network, for computational analysis and prediction. Link prediction as a computational graph analysis method can help us to gain new insight into the network. In this article, after creating a network between cancer and SNPs using SNPedia and Cancer Research UK databases, we evaluated the computational link prediction methods to foresee new SNP-Cancer relationships. Results show that among the popular scoring methods based on network topology, for relation prediction, the preferential attachment (PA) algorithm is the most robust method according to computational and experimental evidence, and some of its computational predictions are corroborated in recent publications. According to the PA predictions, rs1801394-Non-small cell lung cancer, rs4880-Non-small cell lung cancer, and rs1805794-Colorectal cancer are some of the best probable SNP-Cancer associations that have not yet been mentioned in any published article, and they are the most probable candidates for additional laboratory and validation studies. Also, it is feasible to improve the predicting algorithms to produce new predictions in the future.

scholarly journals Possible involvement of the Hedgehog and PDPK1–Akt pathways in the growth and migration of small-cell lung cancer

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110165
Author(s):  
Naiwang Tang ◽  
Bin Hu ◽  
Yin Zhang ◽  
Zhiwei Chen ◽  
Ronghuan Yu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Patient Characteristics ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
And Migration ◽  
Proliferation And Migration

Background Small-cell lung cancer (SCLC) accounts for approximately 15% to 20% of all lung cancers, and it is the leading cause of tumor-related deaths globally. This study explored the molecular mechanisms underlying the development of SCLC. Methods The correlations of phosphoinositide-dependent kinase-1 (PDPK1), p-Akt, and Hedgehog expression with patient characteristics were analyzed using SCLC specimens, and their expression was measured in BEAS-2B cells (control) and the SCLC cell lines H82, H69, H446, H146, and H526. Transfection experiments were performed to inhibit or activate gene expression in cells. We then measured the proliferation and migration of H146 cells. Results PDPK1, p-Akt, and Hedgehog expression was significantly higher in SCLC tissues, and their expression was correlated with patient characteristics. p-Akt expression was significantly correlated with Hedgehog expression. In H146 cells, PDPK1 and p-Akt were significantly upregulated. Silencing of PDPK1 or Akt and inhibition of Hedgehog significantly inhibited the proliferation and migration of H146 cells. PDPK1 and Akt affected Hedgehog expression, but Hedgehog did not affect PDPK1 or p-Akt expression. Conclusions The interaction between the PDPK1–Akt pathway and the Hedgehog pathway influences the prognosis, growth, and migration of SCLC.

scholarly journals MicroRNA-138 Inhibits Cell Growth, Invasion, and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop

2018 ◽  
Vol 26 (3) ◽  
pp. 385-400 ◽  
Author(s):  
Dandan Li ◽  
Changjun He ◽  
Junfeng Wang ◽  
Yanbo Wang ◽  
Jianlong Bu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung

Many studies have shown that downregulation of miR-138 occurs in a variety of cancers including non-small cell lung cancer (NSCLC). However, the precise mechanisms of miR-138 in NSCLC have not been well clarified. In this study, we investigated the biological functions and molecular mechanisms of miR-138 in NSCLC cell lines, discussing whether it could turn out to be a therapeutic biomarker of NSCLC in the future. In our study, we found that miR-138 is downregulated in NSCLC tissues and cell lines. Moreover, the low level of miR-138 was associated with increased expression of SOX4 in NSCLC tissues and cell lines. Upregulation of miR-138 significantly inhibited proliferation of NSCLC cells. In addition, invasion and EMT of NSCLC cells were suppressed by overexpression of miR-138. However, downregulation of miR-138 promoted cell growth and metastasis of NSCLC cells. Bioinformatics analysis predicted that SOX4 was a potential target gene of miR-138. Next, luciferase reporter assay confirmed that miR-138 could directly target SOX4. Consistent with the effect of miR-138, downregulation of SOX4 by siRNA inhibited proliferation, invasion, and EMT of NSCLC cells. Overexpression of SOX4 in NSCLC cells partially reversed the effect of miR-138 mimic. In addition, decreased SOX4 expression could increase the level of miR-138 via upregulation of p53. Introduction of miR-138 dramatically inhibited growth, invasion, and EMT of NSCLC cells through a SOX4/p53 feedback loop.

Association of single nucleotide autophagy‐related protein 5 gene polymorphism rs2245214 with susceptibility to non–small cell lung cancer

2018 ◽  
Vol 120 (2) ◽  
pp. 1924-1931 ◽  
Author(s):  
Mohsen Nikseresht ◽  
Maryam Shahverdi ◽  
Mehdi Dehghani ◽  
Hassan Abidi ◽  
Reza Mahmoudi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Polymorphism ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Related Protein ◽  
Small Cell Lung ◽  
Single Nucleotide

scholarly journals Downregulation of miR-506-3p Facilitates EGFR-TKI Resistance through Induction of Sonic Hedgehog Signaling in Non-Small-Cell Lung Cancer Cell Lines

2020 ◽  
Vol 21 (23) ◽  
pp. 9307
Author(s):  
Inamul Haque ◽  
Hameem I. Kawsar ◽  
Hannah Motes ◽  
Mukut Sharma ◽  
Snigdha Banerjee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Sonic Hedgehog ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Tki Resistance ◽  
Egfr Tki

Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs). Treatment resistance remains the primary obstacle to the successful treatment of NSCLC. Although drug resistance mechanisms have been studied extensively in NSCLC, the regulation of these mechanisms has not been completely understood. Recently, increasing numbers of microRNAs (miRNAs) are implicated in EGFR-TKI resistance, indicating that miRNAs may serve as novel targets and may hold promise as predictive biomarkers for anti-EGFR therapy. MicroRNA-506 (miR-506) has been identified as a tumor suppressor in many cancers, including lung cancer; however, the role of miR-506 in lung cancer chemoresistance has not yet been addressed. Here we report that miR-506-3p expression was markedly reduced in erlotinib-resistant (ER) cells. We identified Sonic Hedgehog (SHH) as a novel target of miR-506-3p, aberrantly activated in ER cells. The ectopic overexpression of miR-506-3p in ER cells downregulates SHH signaling, increases E-cadherin expression, and inhibits the expression of vimentin, thus counteracting the epithelial–mesenchymal transition (EMT)-mediated chemoresistance. Our results advanced our understanding of the molecular mechanisms underlying EGFR-TKI resistance and indicated that the miR-506/SHH axis might represent a novel therapeutic target for future EGFR mutated lung cancer treatment.

LncRNA BRCAT54 inhibits the tumorigenesis of non-small cell lung cancer by binding to RPS9 to transcriptionally regulate JAK-STAT and calcium pathway genes

2020 ◽  
Author(s):  
Wenhan Yang ◽  
Youhui Qian ◽  
Kaiping Gao ◽  
Wenjing Zheng ◽  
Guodong Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Small Cell Lung ◽  
Gene Expressions ◽  
Qrt Pcr ◽  
Pathway Gene

Abstract Objectives: Increasing evidence suggest that long non-coding RNAs (lncRNAs) play critical roles in cancers. However, the expression pattern and underlying mechanisms of lncRNAs in non-small cell lung cancer (NSCLC) remain incompletely understood. This study aimed to elucidate the functions and molecular mechanisms of a certain lncRNA in NSCLC. Methods: LncRNA microarray was performed to identify differential expressed lncRNAs between pre- and postoperation plasma in NSCLC patients. The expression level of candidate lncRNA in NSCLC tissues, plasma and cells was determined by quantitative real-time PCR (qRT-PCR) and in situ hybridization. The functional roles of lncRNA were assessed in vitro and in vivo. Furthermore, RNA pull-down, RNA immunoprecipitation, microarray, qRT-PCR and rescue assays were conducted to explore the mechanism action of lncRNA in NSCLC cells. Results: We identified a novel lncRNA (BRCAT54), which was significantly upregulated in preoperative plasma, NSCLC tissues and NSCLC cells, and its higher expression was associated with better prognosis in patients with NSCLC. Overexpression of BRCAT54 inhibited proliferation, migration and activated apoptosis in NSCLC cells. Conversely, knockdown of BRCAT54 reversed the suppressive effects of BRCAT54. Moreover, overexpression of BRCAT54 repressed NSCLC cell growth in vivo. Mechanistically, BRCAT54 directly bound to RPS9. Knockdown of RPS9 substantially reversed the promoting effects of si-BRCAT54 on cell proliferation and enhanced the inhibitive effect of si-BRCAT54 on BRCAT54 expression. In addition, silencing of RPS9 activated JAK-STAT pathway and suppressed calcium signaling pathway gene expressions. Conclusion: This study identified BRCAT54 as a tumor suppressor in NSCLC. Targeting the BRCAT54 and RPS9 feedback loop might be a novel therapeutic strategy for NSCLC.

C/EBPα expression by immunohistochemistry lacks prognostic or predictive significance in primary resected non-small cell lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7202-7202
Author(s):  
D. B. Costa ◽  
P. Stephenson ◽  
O. Kocher ◽  
D. G. Tenen ◽  
R. H. Feins ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Thoracic Radiation

7202 Background: The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) is down-regulated in a majority of lung cancers. We sought to determine if C/EBPα could be a prognostic or predictive factor in non-small-cell lung cancer (NSCLC). Methods: Our cohort originated from ECOG 3590/4592 (randomized trial of postoperative adjuvant therapy with thoracic radiation or cisplatin and etoposide plus thoracic radiation in patients with completely resected stages II and IIIA NSCLC; and its laboratorial study). 166 tumor samples contained material for immunohistochemical (IHC) analysis of C/EBPα expression. We used a scoring system comparing tumor staining to that of basal bronchial cells (3+). 0 or 1+ (weak) staining suggested lack of, while 2 or 3+ (strong) suggested C/EBPα expression. Our primary outcomes were differences in progression-free and overall survival between the groups with weak or strong staining. Results: Among the 166 patients analyzed for C/EBPα IHC, the median progression free and overall survival were 30.7 and 40.3 months, respectively; which do not differ from the complete E4592 cohort. 92 patient samples (55%) had 0 or 1+ staining, and the remaining 74 (45%) 2 or 3+. The median progression free survival for patients with weak and strong C/EBPα IHC expression was 31.5 and 30.2 months, respectively (p = 0.84). The median overall survival between the weak and strong groups was 47.5 and 38.3 months, respectively (p = 0.54). 10 years after enrollment, 27% (25/92) of patients were alive in the weak, and 24% (18/74) in the strong C/EBPα IHC group. No difference between our primary outcomes by C/EBPα expression was identified. There was no difference in outcome by treatment arm, tumor histology, stage, or patient’s characteristics. There was a trend towards loss of C/EBPα and less differentiated tumor samples (p = 0.07). Conclusions: C/EBPα is a novel tumor suppressor gene in lung cancer with loss of expression in over 50% of NSCLC. However, our data demonstrate that in a subset of patients with resected NSCLC, C/EBPα IHC status is neither a prognostic nor a predictive marker. Further studies are needed to establish the molecular mechanisms of C/EBPα inactivation in lung cancer and its possible role as a new therapeutic target. No significant financial relationships to disclose.

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