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Human bronchial epithelial cells as a good control for evaluation potential therapeutic Notch signaling in non-small cell lung cancer

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Pancewicz J., Bernatowicz, P.L, Golec P.
Progress in Health Sciences
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2018
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vol. 8(1)
7-13
EN
Purpose: Notch signaling is often deregulated in non-small cell lung cancer (NSCLC), but little is known about the initial endogenous mRNA status of Notch ligands and receptors. Therefore, the aim of this study was to evaluate expression level of NOTCH1 receptor and Notch ligands, such as delta like ligands (DLL1, DLL3, DLL4), and jagged ligands (JAG1, JAG2), as well as target gene-hes family bHLH transcription factor 1 (HES1) in diverse NSCLC cell lines. Materials and Methods: We have investigated the mRNA expression of chosen genes by using quantitative real time method (RT-PCR). We compared the results from NSCLC cells with results obtained in non-cancerous human bronchial epithelial cells (HBEpC). We also measured NOTCH1 expression in A549 cells, before and after treatment with γ-secretase inhibitor (GSI). Results: The expression level of NOTCH1, HES1, JAG1 and JAG2 was downregulated when compared to HBEpC. The expression of Notch ligand DLL1 was lower in all cancer cell lines, but mRNA level of DLL3 was elevated in H1299 and A549 cells when related to HBEpC. The mRNA level of DLL4 was higher in H520 and in A549 cell lines. Moreover, the mRNA level of NOTCH1 dropped down after GSI treatment, in addition A549 cells proliferated slower after drug implementation. Conclusions: We conclude that non-cancerous HBEpC cells could serve as a good control for Notch mRNAs expression analysis in NSCLC. Moreover, GSI-treated cells could inhibit proliferation through suppressing NOTCH1 in A549 cells. Keywords: Notch, NSCLC, HBEpC
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Long non-coding RNA and Notch regulation in non-small cell lung cancer

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Pancewicz J.
Progress in Health Sciences
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2020
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vol. 10(1)
108-122
EN
Non-small cell lung cancer is one of the most commonly diagnosed cancer with a very high mortality rate. Trying to understand the mechanisms underlying the progression of this type of cancer, it is necessary to evaluate the changes occurring at molecular level in cancer cells. Besides the widely studied signaling pathways and genes which are dysregulated in NSCLC, there is a large group of non-coding RNAs involved in cancer pathogenesis. Those RNAs are tissue specific heterogeneous class of RNAs that play many functions in physiological condition in cells, nevertheless current data has shown that lncRNAs are also functional in different types of cancer. Moreover, it has been suggest that lncRNAs are involved in cancer progression by controlling key signaling pathways involved in diverse types of tumors. Notch signaling is one of those pathways, very often deregulated in NSCLC. Therefore in this review I summarized recent outcomes according the importance of lncRNAs in regulation of Notch pathway in the pathogenesis of NSCLC.
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