RARβ Promoter Methylation as an Epigenetic Mechanism of Gene Silencing in Non-small Cell Lung Cancer

Author(s):  
A. Dutkowska ◽  
A. Antczak ◽  
D. Pastuszak-Lewandoska ◽  
M. Migdalska-Sęk ◽  
K. H. Czarnecka ◽  
...  
2020 ◽  
Vol 21 (13) ◽  
pp. 4595
Author(s):  
Victoria Sarne ◽  
Samuel Huter ◽  
Sandrina Braunmueller ◽  
Lisa Rakob ◽  
Nico Jacobi ◽  
...  

Specific gene promoter DNA methylation is becoming a powerful epigenetic biomarker in cancer diagnostics. Five genes (CDH1, CDKN2Ap16, RASSF1A, TERT, and WT1) were selected based on their frequently published potential as epigenetic markers. Diagnostic promoter methylation assays were generated based on bisulfite-converted DNA pyrosequencing. The methylation patterns of 144 non-small-cell lung cancer (NSCLC) and 7 healthy control formalin-fixed paraffin-embedded (FFPE) samples were analyzed to evaluate the applicability of the putative diagnostic markers. Statistically significant changes in methylation levels are shown for TERT and WT1. Furthermore, 12 NSCLC and two benign lung cell lines were characterized for promoter methylation. The in vitro tests involved a comparison of promoter methylation in 2D and 3D cultures, as well as therapeutic tests investigating the impact of CDH1/CDKN2Ap16/RASSF1A/TERT/WT1 promoter methylation on sensitivity to tyrosine kinase inhibitor (TKI) and DNA methyl-transferase inhibitor (DNMTI) treatments. We conclude that the selected markers have potential and putative impacts as diagnostic or even predictive marker genes, although a closer examination of the resulting protein expression and pathway regulation is needed.


2015 ◽  
Vol 30 (2) ◽  
pp. 155 ◽  
Author(s):  
Tae-Hyung Kim ◽  
Ji-Yong Moon ◽  
Sang-Heon Kim ◽  
Seung Sam Paik ◽  
Ho Joo Yoon ◽  
...  

2020 ◽  
Vol 8 (8) ◽  
pp. 1616-1628 ◽  
Author(s):  
Menghao Shi ◽  
Jiulong Zhang ◽  
Ziyuan Huang ◽  
Yuying Chen ◽  
Shuang Pan ◽  
...  

A stimuli-responsive nanoplatform achieves successful intracellular siRNA delivery due to a proton sponge effect based on poly(l-histidine) and effective gene silencing in vivo.


Neoplasia ◽  
2003 ◽  
Vol 5 (4) ◽  
pp. 362-366 ◽  
Author(s):  
Jie Li ◽  
Zhongqiu Zhang ◽  
Zunyan Dai ◽  
Anthony P. Popkie ◽  
Christoph Plass ◽  
...  

2015 ◽  
Vol 34 (3) ◽  
pp. 1510-1516 ◽  
Author(s):  
WEIYI HUANG ◽  
WEIQING ZHONG ◽  
JUN XU ◽  
BENHUA SU ◽  
GUANGHUI HUANG ◽  
...  

2021 ◽  
Vol 12 (12) ◽  
pp. 3468-3485
Author(s):  
Noor Hanis Abu Halim ◽  
Norashikin Zakaria ◽  
Kumitaa Theva Das ◽  
Juntang Lin ◽  
Moon Nian Lim ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1523
Author(s):  
Federico Pio Fabrizio ◽  
Angelo Sparaneo ◽  
Andrea Fontana ◽  
Tommaso Mazza ◽  
Paolo Graziano ◽  
...  

The silencing of SPARC (secreted protein acid and rich in cysteine) gene through methylation of its promoter region represents a common event in many solid tumors and it is frequently associated with tumor progression and an aggressive clinical outcome. Anyhow, the data concerning the epigenetic mechanism of SPARC deregulation and its prognostic value in lung cancer are still incomplete. We explored the aberrant methylation of SPARC and its effects in 4 non-small cell lung cancer (NSCLC) cell lines and 59 NSCLC tissues and correlated the methylation levels with clinical-pathological features and disease outcome of patients. In 3 out of 4 tumor cell lines high SPARC methylation levels were observed. An inverse correlation between the epigenetic silencing and SPARC expression was confirmed by 5-Aza-2′-deoxycytidine ((5-Aza-CdR) treatment that also significantly induced a reduction in cell viability, proliferation and tumor cell migration. In tissues, the DNA methylation levels of the SPARC gene were significantly lower in paired non-neoplastic lungs (NLs) and normal lungs distant from tumor (NLDTs) than in NSCLCs (p = 0.002 and p = 0.0034 respectively). A promoter hypermethylation was detected in 68% of squamous cell carcinoma (SqCCs, 17/25) and 56% of adenocarcinoma (ADCs, 19/34), with SqCC showing the highest levels of methylation. Higher SPARC methylation levels were significantly associated with higher mortality risk both in all NSCLCs early stage patients (Hazard Ratio, HR = 1.97; 95% Confidence Interval, CI: 1.32–2.93; p = 0.001) and in those with SqCC (HR = 2.96; 95% CI: 1.43–6.12; p = 0.003). Promoter methylation of SPARC gene should represent an interesting prognostic biomarker in NSCLC, with potential application in the squamous early-stage context. Further research in this setting on larger independent cohorts of lung patients with different histologies and stages of disease are warranted.


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