miR-9-5p Exerts a Dual Role in Cervical Cancer and Targets Transcription Factor TWIST1

Autor: Renske D.M. Steenbergen, Annina P van Splunter, Annelieke Jaspers, Iris A E van der Hoorn, Saskia M Wilting, Iris Babion
Přispěvatelé: Medical Oncology, Pathology, CCA - Cancer biology and immunology, AII - Cancer immunology, CCA - Imaging and biomarkers
Rok vydání: 2020
Předmět:
Zdroj: Cells, 9(1):65. Multidisciplinary Digital Publishing Institute (MDPI)
Cells, 9(1):65. MDPI Multidisciplinary Digital Publishing Institute
Cells
Cells, Vol 9, Iss 1, p 65 (2019)
Volume 9
Issue 1
Babion, I, Jaspers, A, van Splunter, A P, van der Hoorn, I A E, Wilting, S M & Steenbergen, R D M 2020, ' MiR-9-5p exerts a dual role in cervical cancer and targets transcription factor TWIST1 ', Cells, vol. 9, no. 1, 65 . https://doi.org/10.3390/cells9010065
ISSN: 2073-4409
Popis: Squamous cell carcinoma (SCC) and adenocarcinoma (AC) represent the major cervical cancer histotypes. Both histotypes are caused by infection with high-risk HPV (hrHPV) and are associated with deregulated microRNA expression. Histotype-dependent expression has been observed for miR-9-5p, showing increased expression in SCC and low expression in AC. Here, we studied the regulation and functionality of miR-9-5p in cervical SCCs and ACs using cervical tissue samples and hrHPV-containing cell lines. Expression and methylation analysis of cervical tissues revealed that low levels of miR-9-5p in ACs are linked to methylation of its precursor genes, particularly miR-9-1. Stratification of tissue samples and hrHPV-containing cell lines suggested that miR-9-5p depends on both histotype and hrHPV type, with higher expression in SCCs and HPV16-positive cells. MiR-9-5p promoted cell viability and anchorage independence in cervical cancer cell lines SiHa (SCC, HPV16) and CaSki (metastasized SCC, HPV16), while it played a tumor suppressive role in HeLa (AC, HPV18). TWIST1, a transcription factor involved in epithelial-to-mesenchymal transition (EMT), was established as a novel miR-9-5p target. Our results show that miR-9-5p plays a dual role in cervical cancer in a histotype- and hrHPV type-dependent manner. MiR-9-5p mediated silencing of TWIST1 suggests two distinct mechanisms towards EMT in cervical cancer.
Databáze: OpenAIRE