Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer

• Verfasst von: Ceppi, Paolo [VerfasserIn]
• Verfasst von: Mudduluru, Giridhar [VerfasserIn]
• Verfasst von: Kumarswamy, Regalla [VerfasserIn]
• Verfasst von: Rapa, Ida [VerfasserIn]
• Verfasst von: Scagliotti, Giorgio V. [VerfasserIn]
• Verfasst von: Papotti, Mauro [VerfasserIn]
• Verfasst von: Allgayer, Heike [VerfasserIn]
• Titel: Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer
• Verf.angabe: Paolo Ceppi, Giridhar Mudduluru, Regalla Kumarswamy, Ida Rapa, Giorgio V. Scagliotti, Mauro Papotti, and Heike Allgayer
• E-Jahr: 2010
• Jahr: 8 September 2010
• Umfang: 10 S.
• Fussnoten: Gesehen am 30.01.2023
• Titel Quelle: Enthalten in: Molecular cancer research
• Ort Quelle: Philadelphia, Pa. : AACR, 2002
• Jahr Quelle: 2010
• Band/Heft Quelle: 8(2010), 9, Seite 1207-1216
• ISSN Quelle: 1557-3125
• DOI: doi:10.1158/1541-7786.MCR-10-0052
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Animals
• Sach-SW: Antibodies, Monoclonal
• Sach-SW: Antibodies, Monoclonal, Humanized
• Sach-SW: Cadherins
• Sach-SW: Carcinoma, Non-Small-Cell Lung
• Sach-SW: Cell Line, Tumor
• Sach-SW: Cetuximab
• Sach-SW: Chick Embryo
• Sach-SW: Cisplatin
• Sach-SW: DNA Methylation
• Sach-SW: Drug Resistance, Neoplasm
• Sach-SW: Female
• Sach-SW: Gene Expression Regulation, Neoplastic
• Sach-SW: Humans
• Sach-SW: Lung Neoplasms
• Sach-SW: Lymph Nodes
• Sach-SW: Male
• Sach-SW: Mesoderm
• Sach-SW: MicroRNAs
• Sach-SW: Middle Aged
• Sach-SW: Neoplasm Invasiveness
• Sach-SW: Neoplasm Metastasis
• Sach-SW: Phenotype
• Sach-SW: Promoter Regions, Genetic
• K10plus-PPN: 1832682315

Abstract

The development of metastases is the main reason for cancer-related death in non-small cell lung cancer (NSCLC). The initiation of metastasis involves an increase in cell motility mediated by the loss of cell-cell adhesion caused by E-cadherin repression, in a process commonly known as epithelial-to-mesenchymal transition. A role for microRNA-200 family members in regulating epithelial-to-mesenchymal transition has recently been indicated but data about their expression in lung tumors is still unavailable. The present study investigated the expression of miR-200c in a panel of NSCLC cell lines (n = 9), and a strong inverse correlation with invasion was detected. Reintroduction of miR-200c into highly invasive/aggressive NSCLC cells induced a loss of the mesenchymal phenotype by restoring E-cadherin and reducing N-cadherin expression, and inhibited in vitro cell invasion as well as in vivo metastasis formation. Moreover, miR-200c overexpression restored the sensitivity of NCI-H1299 cells to cisplatin and cetuximab. Hypermethylation of the promoter region was found to be responsible for the loss of miR-200c in invasive cells, as evaluated by 5-aza-2'-deoxycytidine treatment, methylation-specific PCR, and bisulfite sequencing. In primary tumor specimens obtained from 69 patients with consecutively resected NSCLC, lower miR-200c expression levels were found to be associated with a poor grade of differentiation (P = 0.04), a higher propensity to lymph node metastases (P < 0.01), and with a lower E-cadherin expression (P = 0.01). These data indicate that the loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype, and that assessment of its expression could contribute to a better clinicopathologic definition of patients with NSCLC.