The let-7 MicroRNA represses cell proliferation pathways in human cells

• Published in: Cancer research (Chicago, Ill.) Vol. 67; no. 16; pp. 7713 - 7722
• Main Authors: JOHNSON, Charles D, ESQUELA-KERSCHER, Aurora, CHIN, Lena, BROWN, David, SLACK, Frank J, STEFANI, Giovanni, BYROM, Mike, KELNAR, Kevin, OVCHARENKO, Dmitriy, WILSON, Mike, XIAOWEI WANG, SHELTON, Jeffrey, SHINGARA, Jaclyn
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.08.2007
• Subjects: Antineoplastic agents; Biological and medical sciences; Caenorhabditis elegans; cdc25 Phosphatases - biosynthesis; cdc25 Phosphatases - genetics; Cell Cycle - genetics; Cell Growth Processes - genetics; Cell Line, Tumor; Cyclin-Dependent Kinase 6 - biosynthesis; Cyclin-Dependent Kinase 6 - genetics; Gene Expression Regulation, Neoplastic; Genes, ras; HeLa Cells; Humans; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Lung - metabolism; Lung - physiology; Medical sciences; Microarray Analysis; MicroRNAs - biosynthesis; MicroRNAs - genetics; Pharmacology. Drug treatments; Transfection; Tumors; Human; Cell proliferation; microRNA; RNA interference; In vitro; Micro RNA
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-07-1083

MicroRNAs play important roles in animal development, cell differentiation, and metabolism and have been implicated in human cancer. The let-7 microRNA controls the timing of cell cycle exit and terminal differentiation in Caenorhabditis elegans and is poorly expressed or deleted in human lung tumors. Here, we show that let-7 is highly expressed in normal lung tissue, and that inhibiting let-7 function leads to increased cell division in A549 lung cancer cells. Overexpression of let-7 in cancer cell lines alters cell cycle progression and reduces cell division, providing evidence that let-7 functions as a tumor suppressor in lung cells. let-7 was previously shown to regulate the expression of the RAS lung cancer oncogenes, and our work now shows that multiple genes involved in cell cycle and cell division functions are also directly or indirectly repressed by let-7. This work reveals the let-7 microRNA to be a master regulator of cell proliferation pathways.