The let-7 microRNA represses cell proliferation pathways in human cells.
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.
Johnson
Charles D
CD
Asuragen, Inc, Texas, USA.
Esquela-Kerscher
Aurora
A
Stefani
Giovanni
G
Byrom
Mike
M
Kelnar
Kevin
K
Ovcharenko
Dmitriy
D
Wilson
Mike
M
Wang
Xiaowei
X
Shelton
Jeffrey
J
Shingara
Jaclyn
J
Chin
Lena
L
Brown
David
D
Slack
Frank J
FJ
D002453:Cell Cycle / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D051361:Cyclin-Dependent Kinase 6 / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006367:HeLa Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000502:physiology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D046228:Microarray Analysis; D014162:Transfection; D020687:cdc25 Phosphatases / Q000096:biosynthesis / Q000235:genetics
D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases