Long non-coding RNA CCAT1 is overexpressed in endometrial cancer and regulates growth and transcriptome of endometrial adenocarcinoma cells

Background Recent studies suggested the long non-coding RNA (lncRNA) Colon cancer associated transcript-1 (CCAT1) to act as putative oncogene. 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 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 for transciptome analyses.

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 endometrial 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 and reduced their colony formation ability. Affymetrix microarray and Ingenuity pathway analyses revealed a set regulated genes in transfected ERa-negative HEC-1B cells forming a network controlled by the key regulators TNF and TP53, including genes known to be involved in growth control. 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 Our data suggest CCAT1 to exert oncogenic functions in endometrial cancer and encourage further studies to examine to what extent it might be a potential therapy target.

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Publication History

Article published online:
07 October 2020