| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | The International Journal of Biochemistry & Cell Biology | ||||
| Publisher: | PERGAMON-ELSEVIER SCIENCE LTD | ||||
| Place of Publication: | OXFORD | ||||
| Volume: | 122 | ||||
| Page Range: | p. 105740 | ||||
| Date: | 2020 | ||||
| Institutions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) | ||||
| Identification Number: |
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| Keywords: | POOR-PROGNOSIS; OVARIAN-CANCER; PROLIFERATION; METASTASIS; GANKYRIN; PROGRESS; lncRNA; CCAT1; DNA microarray; HEC-1B; RL95/2; Oncogene | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 50066 |
Web of ScienceAbstract
Background: Long non-coding RNAs (lncRNAs) play important roles in regulation of gene expression and are involved in pathogenesis of different diseases including cancer. Recent studies suggested the lncRNA Colon cancer associated transcript-1 (CCAT1) to act as putative oncogene. In this study, to elucidate the role of this lncRNA in endometrial cancer, we examined its expression in normal ...
Abstract
Background: Long non-coding RNAs (lncRNAs) play important roles in regulation of gene expression and are involved in pathogenesis of different diseases including cancer. Recent studies suggested the lncRNA Colon cancer associated transcript-1 (CCAT1) to act as putative oncogene. In this study, to elucidate the role of this lncRNA in endometrial cancer, we examined its expression in normal endometrium and type 1 endometrial cancer and knocked down its expression in endometrial cancer cell lines followed by transcriptome and pathway analyses. Methods: CCAT1 expression was examined in 100 tissue samples of normal endometrium and type 1 endometrial cancer tissues by means of RT-qPCR. Knockdown of CCAT1 expression in HEC-1B and RL95/2 endometrial cancer cells was performed by siRNA transfection. Affymetrix GeneChip arrays were used to elucidate the effect of both lncRNAs on the transcriptome of these cell lines. Results: Median CCAT1 expression was found to be 9.3-fold higher in endometrial cancer when compared to normal endometrium (p < 0.05). In contrast to premenopausal endometrium and G1, G2 and G3 graded en-dometrial cancer, CCAT1 expression was nearly absent in postmenopausal tissue. Knockdown of CCAT1 by transient siRNA transfection significantly reduced proliferation of HEC-1B cancer cells in vitro by 35.5 % 6 days after transfection and notably reduced their colony formation ability. Affymetrix microarray and Ingenuity pathway analyses revealed a set of up- or down-regulated genes in transfected ER alpha-negative HEC-1B cells forming a network controlled by the key regulators TNF and TP53, including genes known to be involved in growth control, providing putative molecular mechanisms underlying the observed growth inhibition of HEC-1B cells. In contrast, CCAT1 knockdown in ERa-positive RL95/2 cells did not significantly affect proliferation, but resulted in down-regulation of a network of ERa target genes. Conclusions: Given that the lncRNA CCAT1 was found to be overexpressed in endometrial cancer, affected the growth of HEC-1B cells and the expression of growth regulatory genes, our data suggest CCAT1 to exert on-cogenic functions in endometrial cancer and encourage further studies to examine to what extent this lncRNA might be a potential therapy target in this cancer entity.
Metadata last modified: 11 Oct 2021 12:51
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