The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis.
MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that are important in many biological processes. Although the oncogenic and tumour-suppressive functions of several miRNAs have been characterized, the role of miRNAs in mediating tumour metastasis was addressed only recently and still remains largely unexplored. To identify potential metastasis-promoting miRNAs, we set up a genetic screen using a non-metastatic, human breast tumour cell line that was transduced with a miRNA-expression library and subjected to a trans-well migration assay. We found that human miR-373 and miR-520c stimulated cancer cell migration and invasion in vitro and in vivo, and that certain cancer cell lines depend on endogenous miR-373 activity to migrate efficiently. Mechanistically, the migration phenotype of miR-373 and miR-520c can be explained by suppression of CD44. We found significant upregulation of miR-373 in clinical breast cancer metastasis samples that correlated inversely with CD44 expression. Taken together, our findings indicate that miRNAs are involved in tumour migration and invasion, and implicate miR-373 and miR-520c as metastasis-promoting miRNAs.
Huang
Qihong
Q
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. qhuang@wistar.org
Gumireddy
Kiranmai
K
Schrier
Mariette
M
le Sage
Carlos
C
Nagel
Remco
R
Nair
Suresh
S
Egan
David A
DA
Li
Anping
A
Huang
Guanghua
G
Klein-Szanto
Andres J
AJ
Gimotty
Phyllis A
PA
Katsaros
Dionyssios
D
Coukos
George
G
Zhang
Lin
L
Puré
Ellen
E
Agami
Reuven
R
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000502:physiology*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000096:biosynthesis / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous
D018960:Hyaluronan Receptors; D035683:MicroRNAs