Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer.
p130Cas regulates cancer progression by driving tyrosine receptor kinase signaling. Tight regulation of p130Cas expression is necessary for survival, apoptosis, and maintenance of cell motility in various cell types. Several studies revealed that transcriptional and post-translational control of p130Cas are important for maintenance of its expression and activity. To explore novel regulatory mechanisms of p130Cas expression, we studied the effect of microRNAs (miRs) on p130Cas expression in human breast cancer MCF7 cells. Here, we provide experimental evidence that miR-362-3p and miR-329 perform a tumor-suppressive function and their expression is downregulated in human breast cancer. miR-362-3p and miR-329 inhibited cellular proliferation, migration, and invasion, thereby suppressing tumor growth, by downregulating p130Cas. Ectopic expression of p130Cas attenuated the inhibitory effects of the two miRs on tumor progression. Relative expression levels of miR-362-3p/329 and p130Cas between normal and breast cancer correlated inversely; miR-362-3p/329 expression was decreased, whereas that of p130Cas increased in breast cancers. Furthermore, we showed that downregulation of miR-362-3p and miR-329 was caused by differential DNA methylation of miR genes. Enhanced DNA methylation (according to methylation-specific PCR) was responsible for downregulation of miR-362-3p and miR-329 in breast cancer. Taken together, these findings point to a novel role for miR-362-3p and miR-329 as tumor suppressors; the miR-362-3p/miR-329-p130Cas axis seemingly has a crucial role in breast cancer progression. Thus, modulation of miR-362-3p/miR-329 may be a novel therapeutic strategy against breast cancer.
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
H
H
Kang
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
C
C
Kim
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
H
H
Lee
Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
J G
JG
Rho
Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, South Korea.
J-W
JW
Seo
Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, South Korea.
J-W
JW
Nam
Department of Life Science, Bio Imaging and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, South Korea.
W K
WK
Song
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.|Cancer Evolution Center, College of Medicine, Catholic University of Korea, Seoul, South Korea.
S W
SW
Nam
Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
W
W
Kim
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea.|Cancer Evolution Center, College of Medicine, Catholic University of Korea, Seoul, South Korea.
E K
EK
Lee
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D050719:Crk-Associated Substrate Protein / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D034622:RNA Interference
D050719:Crk-Associated Substrate Protein; C584396:MIRN329 microRNA, human; C581582:MIRN362 microRNA, human; D035683:MicroRNAs