PMID- 31060342 OWN - NLM STAT- MEDLINE DCOM- 20190821 LR - 20200225 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 9 DP - 2019 May 5 TI - Molecular Signature of Prospero Homeobox 1 (PROX1) in Follicular Thyroid Carcinoma Cells. LID - 10.3390/ijms20092212 [doi] LID - 2212 AB - The prospero homeobox 1 (PROX1) transcription factor is a product of one of the lymphangiogenesis master genes. It has also been suggested to play a role in carcinogenesis, although its precise role in tumour development and metastasis remains unclear. The aim of this study was to gain more knowledge on the PROX1 function in thyroid tumorigenesis. Follicular thyroid cancer-derived cells-CGTH-W-1-were transfected with PROX1-siRNA (small interfering RNA) and their proliferation, cell cycle, apoptosis and motility were then analysed. The transcriptional signature of PROX1 depletion was determined using RNA-Sequencing (RNA-Seq) and the expression of relevant genes was further validated using reverse transcriptase quantitative PCR (RT-qPCR), Western blot and immunocytochemistry. PROX1 depletion resulted in a decreased cell motility, with both migratory and invasive potential being significantly reduced. The cell morphology was also affected, while the other studied cancer-related cell characteristics were not significantly altered. RNA-seq analysis revealed significant changes in the expression of transcripts encoding genes involved in both motility and cytoskeleton organization. Our transcriptional analysis of PROX1-depleted follicular thyroid carcinoma cells followed by functional and phenotypical analyses provide, for the first time, evidence that PROX1 plays an important role in the metastasis of thyroid cancer cells by regulating genes involved in focal adhesion and cytoskeleton organization in tumour cells. FAU - Rudzinska, Magdalena AU - Rudzinska M AD - Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland. magdda.rudzinska@gmail.com. FAU - Grzanka, Malgorzata AU - Grzanka M AD - Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland. mgrzanka@cmkp.edu.pl. FAU - Stachurska, Anna AU - Stachurska A AD - Department of Immunohematology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland. astachurska@cmkp.edu.pl. FAU - Mikula, Michal AU - Mikula M AD - Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland. mikula.michal@gmail.com. FAU - Paczkowska, Katarzyna AU - Paczkowska K AD - Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland. paczkowska.km@gmail.com. FAU - Stepien, Tomasz AU - Stepien T AD - Clinic of Endocrinological and General Surgery, Medical University of Lodz, 93-513 Lodz, Poland. tomsamaz@wp.pl. FAU - Paziewska, Agnieszka AU - Paziewska A AD - Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland. apaziewska@cmkp.edu.pl. FAU - Ostrowski, Jerzy AU - Ostrowski J AD - Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland. jostrow@warman.com.pl. AD - Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland. jostrow@warman.com.pl. FAU - Czarnocka, Barbara AU - Czarnocka B AD - Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland. bczarnocka@cmkp.edu.pl. LA - eng GR - 2013/11/N/NZ5/03394 (to M.R.) and 2012/07/B/ NZ5/02444 (to B.C.)/The National Science Center, Poland/ PT - Journal Article DEP - 20190505 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers, Tumor) RN - 0 (Homeodomain Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Suppressor Proteins) RN - 0 (prospero-related homeobox 1 protein) MH - Adenocarcinoma, Follicular/*genetics/pathology MH - Apoptosis/genetics MH - Biomarkers, Tumor MH - Biopsy MH - Cell Cycle/genetics MH - Cell Line, Tumor MH - Cell Movement MH - Cell Survival/genetics MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - High-Throughput Nucleotide Sequencing MH - Homeodomain Proteins/*genetics MH - Humans MH - Immunohistochemistry MH - RNA, Small Interfering/genetics MH - Transcriptome MH - Tumor Suppressor Proteins/*genetics PMC - PMC6539481 OTO - NOTNLM OT - PROX1 OT - RNA-seq OT - cytoskeleton OT - follicular thyroid carcinoma OT - invasion OT - migration COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results. EDAT- 2019/05/08 06:00 MHDA- 2019/08/23 06:00 PMCR- 2019/05/01 CRDT- 2019/05/08 06:00 PHST- 2019/03/13 00:00 [received] PHST- 2019/04/24 00:00 [revised] PHST- 2019/04/28 00:00 [accepted] PHST- 2019/05/08 06:00 [entrez] PHST- 2019/05/08 06:00 [pubmed] PHST- 2019/08/23 06:00 [medline] PHST- 2019/05/01 00:00 [pmc-release] AID - ijms20092212 [pii] AID - ijms-20-02212 [pii] AID - 10.3390/ijms20092212 [doi] PST - epublish SO - Int J Mol Sci. 2019 May 5;20(9):2212. doi: 10.3390/ijms20092212.