Endometrial cancer (EC) is the second most common malignancy of female genitals after cervical cancer worldwide. According to IARC (International Agency for Research on Cancer), in 2020 only more than 400,000 cases and almost 100,000 deaths were reported . As this malignancy poses a serious threat to global health, it has gained global research attention: almost 14,000 original articles on this matter were published from 1900 to 2020 and this number increases continuously . During the greater share of the aforementioned period scholars’ understanding of EC was strictly constrained and dictated by histopathological representation of the disease: type I endometrioid tumours were associated with oestrogen excess, obesity and hormone-receptor positivity, whereas type II non-endometrioid (predominantly serous) ones were less common, lacked hormone-dependency and were labelled with rather a poor prognosis. This classical perception of EC was challenged in 2013 by a notable paper published in Nature when a completely new light shed on the disease shifted the recognition of EC from histology to genetics with even a thorough reclassification proposed .
With the introduction of genetic approach to cancer – as the shift towards genetics is not limited to EC only – some novel research pathways came into exploration, including the analysis of various aspects of human genome and their potential role in carcinogenesis. It became clear that only less than 2% of DNA is represented by mRNA and bares a substantial protein-coding potential which suggested that genes ‘operate’ in a so called ‘plethora of junk DNA’ . The vast majority of human genome is transcribed into a ‘dark matter’ which was initially believed to be only a ‘transcriptional noise’. However, these inter-genic regions proved to have a considerable significance and have rightly drawn major scientific enthusiasm in recent years [, ]. The beforementioned ‘dark matter’ includes, among many others, long non-coding RNA (lncRNA) which is defined as transcripts greater than 200 nucleotides with no evident ability of being translated into protein. Although the role of lncRNA has not been fully elucidated yet, it is well known that it takes a vital part in numerous biological phenomena like epigenetic regulation, genetic imprinting, cell apoptosis and differentiation and even cell cycle control system [, , , , , , ]. Moreover, it regulates RNA maturation, intercellular transport and formation of ribonucleoprotein complexes .
It has been also demonstrated, that lncRNA may promote the growth of endometrial tissue outside the uterine cavity and thus it may contribute to development of endometriosis . According to the growing body of literature, primary differences in lncRNA expression have also been found in various types of cancer [6, , , , ]. Furthermore, lncRNA sequences have been studied in EC with a conclusion that some of these non-coding transcripts may be implemented as both diagnostic and prognostic biomarkers of this malignancy [4, , ].
The first in-depth paper on various subtypes of lncRNA in EC was published by Zhai et al. in 2015 . In this study authors have identified 53 distinct lncRNA sequences which expressions statistically significantly differed in carcinomatous endometrium and cancer-free one. Differences in expression concerned also signalling pathways, cell components and numerous other molecular features.
Recent literature data suggest that the following lncRNA sequences are associated with endometrial cancer: ASLNC04080 (SNHG12 – small nucleolar RNA host gene 12) , H19 (human H19 gene) [, , ], OVAAL (ovarian adenocarcinoma amplified lncRNA) , CASC2 (cancer susceptibility candidate 2) , MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) , HOTAIR (HOX transcript antisense RNA) , SRA (steroid receptor RNA activator) , Linc-RoR (large intergenic non-coding ribonucleic acids-regulator of programming) , LIN00261 , LIN00672 , 7-lncRNA , and many others. It has also been proven, that long non-coding transcripts play some role in proliferation and migration of endometrial cancer cells . Some authors even suggest employing a special algorithm that clusters specific triplets of mRNA, lncRNA and miRNA to better identify the risk of this cancer which may also benefit in deeper understanding of transcriptome regulatory mechanisms in this disease .
Although, as presented above, numerous lncRNA sequences are somehow correlated with EC, the exact meaning and context of this interaction still remains unclear and calls for elucidation. This paper is designed to expand the still vague and uncomplete knowledge of the role of lncRNA in EC. Following lncRNA sequences have been selected for the study: FAM3D-AS1, LINC01230, LINC01315 and LINC01468. There is little or no available literature data on these lncRNAs, and until now none of them has been studied in endometrial cancer.