MiRNA-200C expression in Fanconi anemia pathway functionally deficient lung cancers

• Published in: Scientific reports Vol. 11; no. 1; p. 4420
• Main Authors: Duan, Wenrui, Tang, Shirley, Gao, Li, Dotts, Kathleen, Fink, Andrew, Kalvala, Arjun, Aguila, Brittany, Wang, Qi-En, Villalona-Calero, Miguel A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24-02-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1612/1350; 631/67/68; A549 Cells; Anemia; Cadherins - genetics; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell Proliferation - genetics; Deoxyribonucleic acid; DNA; DNA damage; E-cadherin; Epithelial-Mesenchymal Transition - genetics; Fanconi Anemia - genetics; Fanconi syndrome; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Homeodomain Proteins - genetics; Homologous recombination; Humanities and Social Sciences; Humans; Lung cancer; Lung Neoplasms; Mesenchyme; MicroRNAs; MicroRNAs - genetics; miRNA; multidisciplinary; Poly(ADP-ribose) polymerase; Science; Science (multidisciplinary); Signal Transduction - genetics; Transcription factors; Tumors; Up-Regulation - genetics; Zinc Finger E-box Binding Homeobox 2 - genetics; Zinc Finger E-box-Binding Homeobox 1 - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-83884-9

The Fanconi Anemia (FA) pathway is essential for human cells to maintain genomic integrity following DNA damage. This pathway is involved in repairing damaged DNA through homologous recombination. Cancers with a defective FA pathway are expected to be more sensitive to cross-link based therapy or PARP inhibitors. To evaluate downstream effectors of the FA pathway, we studied the expression of 734 different micro RNAs (miRNA) using NanoString nCounter miRNA array in two FA defective lung cancer cells and matched control cells, along with two lung tumors and matched non-tumor tissue samples that were deficient in the FA pathway. Selected miRNA expression was validated with real-time PCR analysis. Among 734 different miRNAs, a cluster of microRNAs were found to be up-regulated including an important cancer related micro RNA, miR-200C. MiRNA-200C has been reported as a negative regulator of epithelial-mesenchymal transition (EMT) and inhibits cell migration and invasion by promoting the upregulation of E-cadherin through targeting ZEB1 and ZEB2 transcription factors. miRNA-200C was increased in the FA defective lung cancers as compared to controls. AmpliSeq analysis showed significant reduction in ZEB1 and ZEB2 mRNA expression. Our findings indicate the miRNA-200C potentially play a very important role in FA pathway downstream regulation.