scholarly journals The Effects of Lentivirus-Mediated Gene Silencing of RARβ on the Stemness Capability of Non-Small Cell Lung Cancer

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


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

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1994 ◽  
Author(s):  
Daniel P. Feldmann ◽  
Joshua Heyza ◽  
Christoph M. Zimmermann ◽  
Steve M. Patrick ◽  
Olivia M. Merkel

Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an alternative to small molecule inhibitors, small interfering RNA (siRNA) has often been described to be more efficient in interrupting protein–protein interactions. The goal of this study was therefore to determine whether biocompatible nanoparticles consisting of an amphiphilic triblock copolymer (polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG)) and carrying siRNA targeted to ERCC1 and XPF made by microfluidic assembly are capable of efficient gene silencing and able to sensitize lung cancer cells to cisplatin. First, we show that our PEI-PCL-PEG micelleplexes carrying ERCC1 and XPF siRNA efficiently knocked down ERCC1/XPF protein expression to the same extent as the standard siRNA transfection reagent, Lipofectamine. Second, we show that our siRNA-carrying nanoparticles enhanced platinum sensitivity in a p53 wildtype model of non-small cell lung cancer in vitro. Our results suggest that nanoparticle-mediated targeting of ERCC1/XPF is feasible and could represent a novel therapeutic strategy for targeting ERCC1/XPF in vivo.


2015 ◽  
Vol 396 (3) ◽  
pp. 225-234 ◽  
Author(s):  
Davide Sartini ◽  
Riccardo Seta ◽  
Valentina Pozzi ◽  
Stefano Morganti ◽  
Corrado Rubini ◽  
...  

Abstract Lung cancer is the second most commonly diagnosed neoplasm, and represents the leading cause of tumour death worldwide. As patients are often diagnosed at a late stage, current therapeutic strategies have limited effectiveness and the prognosis remains poor. Successful treatment depends on early diagnosis and knowledge concerning molecular mechanisms underlying lung carcinogenesis. In the present study, we focused on nicotinamide N-methyltransferase (NNMT), which is overexpressed in several malignancies. First, we analysed NNMT expression in a cohort of 36 patients with non-small cell lung cancer (NSCLC) by immunohistochemistry. Subsequently, we examined NNMT expression levels in the human lung cancer cell line A549 by Real-Time PCR, Western blot and catalytic activity assay, and evaluated the effect of NNMT knockdown on cell proliferation and anchorage-independent cell growth by MTT and soft agar colony formation assays, respectively. NSCLC displayed higher NNMT expression levels compared to both tumour-adjacent and surrounding tissue. Moreover, shRNA-mediated gene silencing of NNMT led to a significant inhibition of cell proliferation and colony formation ability on soft agar. Our results show that the downregulation of NNMT significantly reduced in vitro tumorigenicity of A549 cells and suggest that NNMT could represent an interesting molecular target for lung cancer therapy.


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