Different levels of let-7d expression modulate response of FaDu cells to irradiation and chemotherapeutics

Lamperska, Katarzyna; Kolenda, Tomasz; Teresiak, Anna; Kowalik, Anna; Kruszyna-Mochalska, Marta; Jackowiak, W.; Bliźniak, Renata; Przybyła, Weronika; Kapałczyńska, Marta; Kozlowski, Piotr

doi:10.1371/journal.pone.0180265

Cited by 20 publications

(17 citation statements)

References 48 publications

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“…Direct targets of let-7 include oncogenes such as RAS and HMGA2 [23,32]. In the present study, we found expression of let-7d was lower in breast cancer tissue than in normal breast tissue.…”

Section: Discussionsupporting

confidence: 52%

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

Wei

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) regulate the expressions of cancer-related genes, and are involved in the development and progression of various human cancers. Here, we performed further analyses to determine whether let-7d is functionally linked to Jab1 in breast cancer. Methods: In situ hybridization and immunohistochemical analyses were used to determine the level of let-7d and Jab1 in breast cancer clinical specimens and its correlation with clinicopathological data. Let-7d overexpressing breast cancer cell lines combined with mouse models bearing cell-derived xenografts were used to assess the functional role of let-7d both in vitro and in vivo. Results: In this study, we found that let-7d was downregulated in breast cancer tissues, coupled with the elevations of Jab1 protein expressions, compared with paired adjacent noncancerous breast tissues. Let-7d overexpression significantly suppressed the proliferation and invasion in MCF-7 and MDA-MB-231 cells. Dual luciferase reporter assay indicated that Jab1 was the direct target of let-7d. Stepwise studies from in vitro and in vivo experiments indicated that let-7d overexpression inhibited cell growth and decreased Jab1 expressions in breast cancer cells and nude mice tumor tissues. Statistical analyses demonstrated that breast cancer patients with low levels of let-7d or high levels of Jab1 had a significant correlation with worse prognosis. Conclusion: These findings provide novel insights into molecular mechanism of let-7d and Jab1 in tumor development and progression of breast cancer, and thus let-7d/Jab1 are novel potential therapeutic targets for breast cancer patients.

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Section: Discussionsupporting

confidence: 52%

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

Wei

Liu

et al. 2018

Cell Physiol Biochem

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“…The SCC-040 and SCC-25 cell lines were maintained according to the instructions from the DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Leibniz Institut, Berlin, Germany). The FaDu cell line was cultured, as described previously [17]. Cal27 cell line was maintained according to the instructions from the ATCC (American Type Culture Collection, Manassas, VA, USA).…”

Section: Methodsmentioning

confidence: 99%

lncRNA Expression after Irradiation and Chemoexposure of HNSCC Cell Lines

Guglas

Kolenda

Teresiak

et al. 2018

ncRNA

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world. To improve the quality of diagnostics and patients’ treatment, new and effective biomarkers are needed. Recent studies have shown that the expression level of different types of long non-coding RNAs (lncRNAs) is dysregulated in HNSCC and correlates with many biological processes. In this study, the response of lncRNAs in HNSCC cell lines after exposure to irradiation and cytotoxic drugs was examined. The SCC-040, SCC-25, FaDu, and Cal27 cell lines were treated with different radiation doses as well as exposed to cisplatin and doxorubicin. The expression changes of lncRNAs after exposure to these agents were checked by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Target prediction was performed using available online tools and classified into specific biological processes and cellular pathways. The results indicated that the irradiation, as well as chemoexposure, causes changes in lncRNA expression and the effect depends on the cell line, type of agents as well as their dose. After irradiation using the dose of 5 Gy significant dysregulation of 4 lncRNAs, 10 Gy-5 lncRNAs, and 20 Gy-3 lncRNAs, respectively, were observed in all cell lines. Only lncRNAs Zfhx2as was down-regulated in all cell lines independently of the dose used. After cisplatin exposure, 14 lncRNAs showed lower and only two higher expressions. Doxorubicin resulted in lower expressions of eight and increased four of lncRNAs. Common effects of cytotoxic drugs were observed in the case of antiPEG11, BACE1AS, PCGEM1, and ST7OT. Analysis of the predicted targets for dysregulated lncRNAs indicated that they are involved in important biological processes, regulating cellular pathways connected with direct response to irradiation or chemoexposure, cellular phenotype, cancer initiating cells, and angiogenesis. Both irradiation and chemoexposure caused specific changes in lncRNAs expression. However, the common effect is potentially important for cellular response to the stress and survival. Further study will show if lncRNAs are useful tools in patients’ treatment monitoring.

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“…lncRNAs are a class of functional RNA molecules over 200-nucleotides long that modulate the activity of transcription factors and regulate changes in the chromatin structure despite not being translated into proteins. Previous studies suggest that lncRNAs have the potential to greatly improve the diagnosis, prognosis and targeted treatment of HNSCC [5,6,7,8].…”

Section: Introductionmentioning

confidence: 99%

EGOT lncRNA in head and neck squamous cell carcinomas

Kolenda¹,

Kopczyńska²,

Guglas³

et al. 2018

pjp

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Head and neck squamous cell carcinomas (HNSCCs) are one of the most challenging cancers to cure. In this study, we focused on eosinophil granule ontogeny transcript (EGOT), a transcriptional regulator of granule protein expression during eosinophil development that has been previously associated with cancers. Expression levels of EGOT and other selected genes as well as clinical pathology data from HNSCC samples, were obtained from The Cancer Genome Atlas (TCGA) and analysed using GraphPad Prism 5. Our results indicated that the expression of EGOT is slightly down-regulated in HNSCC, depending on tumour grade and location, and is only up-regulated in grade 4 tumours and those located in the pharynx. EGOT expression levels were found to vary according to age, N-stage, grade, lymph node dissection and human papillomavirus (HPV) infection. Patients with higher levels of EGOT expression have longer disease-free survival and overall survival outcomes. Further analysis revealed that EGOT targets are associated with cell division, proliferation, protein modification, drug response and cell motility. Taken together, our findings suggest that the EGOT is involved in the progression of HSNCC and seems particularly associated with virus-related forms of HNSCC.

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Different levels of let-7d expression modulate response of FaDu cells to irradiation and chemotherapeutics

Cited by 20 publications

References 48 publications

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

lncRNA Expression after Irradiation and Chemoexposure of HNSCC Cell Lines

EGOT lncRNA in head and neck squamous cell carcinomas

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