**1. Introduction**

Endometriosis is a disorder characterized by the presence of endometrial tissue outside of the uterine cavity, most often attached to organs of the peritoneal cavity [1]. As a common gynecological disorder affecting 6–10% of reproductive age women, endometriosis presents a significant burden on affected patients and society. However, the pathogenesis of the disease is still not well defined. The most accepted explanation for the origin of the cells from which endometriosis lesions develop is retrograde menstruation, whereby endometrial cells flow out into the peritoneal cavity via the fallopian tubes [1]. In order to establish a lesion, endometrial cells in the peritoneal cavity must adhere, implant, and differentiate while avoiding the immune system. Thus, complex interactions between molecular, humoral, immune, genetic and epigenetic signals must occur to support the development, growth and persistence of a lesion [2].

The advent of next-generation sequencing has accelerated identification of changes in the transcriptome, genome and epigenome in the pathogenesis of human diseases including

**Citation:** Yotova, I.; Hudson, Q.J.; Pauler, F.M.; Proestling, K.; Haslinger, I.; Kuessel, L.; Perricos, A.; Husslein, H.; Wenzl, R. *LINC01133* Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line. *Int. J. Mol. Sci.* **2021**, *22*, 8385. https://doi.org/10.3390/ijms22168385

Academic Editor: Antonio Simone Laganà

Received: 23 June 2021 Accepted: 1 August 2021 Published: 4 August 2021

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endometriosis. In recent years, it has become clear that interactions between proteincoding (mRNA) and non-coding transcripts such as long-non-coding RNAs (LncRNAs) can influence the development of disease.

LncRNAs are a class of RNAs greater than 200 nucleotides in length that show similar RNA biology features to mRNAs but do not code for a protein [3]. LncRNA can be transcribed from different genomic regions, including introns, exons, and intergenic regions. Around 30,000 lncRNAs have been identified in humans and mice [4], but only a fraction of these have so far been demonstrated to be functional. LncRNAs are less evolutionally conserved than mRNA [5], and are thought to form a complex tertiary structure when binding DNA, RNA and proteins that may be required for their function [6]. They may act as epigenetic gene regulators by affecting biological functions in the cell such as the assembly and function of nuclear bodies, the stability and translation of cytoplasmic mRNAs, and signaling pathways [7,8]. LncRNAs have been reported to regulate gene expression in a number of different ways, including targeting chromatin modifiers such as Polycomb repressive complex 2 (PRC2), or by acting as so-called miRNA sponges to bind miRNAs that would otherwise bind other targets thereby affecting their expression [9]. Several studies using patient samples and animal models have reported aberrant expression of long non-coding RNAs in endometriosis [10,11]. A growing body of evidence has identified lncRNAs that can alter cell proliferation, migration, invasion and apoptosis of endometriosis cells [12–14]. The molecular mechanism by which these lncRNAs cause these phenotypes has not been shown in all cases. LncRNAs have also been associated with endometriosis-associated angiogenesis [15], infertility [12] and epithelial to mesenchymal transition (EMT) [16]. EMT is a cellular process where epithelial cells acquire a more invasive mesenchymal phenotype and is associated with the loss of E-cadherin (CDH1) and a gain of N-cadherin (CDH2), and the presence of EMT promoting factors such as TWIST1, SNAIL, SLUG and TGFβ [17,18]. In a pathogenic context, it has been established that EMT is a key process in carcinogenesis, but also plays a less well-characterized role in endometriosis lesion development [19]. Hence, clarifying the role of EMT in endometriosis, and its regulation by pathways that may include lncRNAs remains an important issue in the field.

*LINC01133* is an lncRNA that has recently been identified as a putative prognostic marker for endometrial cancer [20]. It has also been associated with the regulation of EMT in several cancers including cervical [21], breast [22], colorectal [23] and gastric [24]. Given that EMT is also a feature of endometriosis [25] we reasoned that *LINC01133* may also be involved in the pathogenesis of endometriosis, and sought to investigate this in our study.
