*Article LINC01133* **Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line**

**Iveta Yotova 1,\* , Quanah J. Hudson <sup>1</sup> , Florian M. Pauler <sup>2</sup> , Katharina Proestling <sup>1</sup> , Isabella Haslinger <sup>1</sup> , Lorenz Kuessel <sup>1</sup> , Alexandra Perricos <sup>1</sup> , Heinrich Husslein <sup>1</sup> and René Wenzl 1,\***


**Abstract:** Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (*LINC01133*) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that *LINC01133* is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of *LINC01133* in an endometriosis epithelial cell line. Phenotypic assays indicated that *LINC01133* may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with *LINC01133* upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways.

**Keywords:** endometriosis; long noncoding RNAs; lncRNAs; epithelial to mesenchymal transition; EMT; proliferation; migration; cytoskeleton
