KRAS up-regulates the expression of miR-181a, miR-200c and miR-210 in a three-dimensional-specific manner in DLD-1 colorectal cancer cells.
BACKGROUND
We previously found that oncogenic KRAS induces increased expression of microRNAs (miRNAs), such as miR-200c and miR-221/222, in human colorectal cancer (CRC) HCT116 cells in a three-dimensional (3D)-specific manner, however, the regulation of miRNA expression through oncogenic KRAS in other types of CRC remains unclear.


METHODS
The differential expression of 94 cancer-related miRNAs was examined in DLD-1 and DKO-4 cells (DLD-1 cells with a disrupted oncogenic KRAS) in 3D cultures.


RESULTS
Increased miR-15b, miR-16, miR-23a, miR-24, miR-103 and miR-222 expression was observed in 3D and in 2D cultures. Of note, increased miR-181a, miR-200c and miR-210 expression was only observed in 3D cultures. Furthermore, miR-181a and miR-210 were significantly overexpressed in DLD-1 cells in 3D culture compared with those in HCT116 cells, and were significantly overexpressed in human CRC specimens.


CONCLUSIONS
Oncogenic KRAS regulates 3D-specific miRNAs that are possibly associated with CRC development in vivo.
Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Takeharu
T
Ota
Keiko
K
Doi
Takahiro
T
Fujimoto
Yoko
Y
Tanaka
Masahiro
M
Ogawa
Hiroshi
H
Matsuzaki
Masahide
M
Kuroki
Shingo
S
Miyamoto
Senji
S
Shirasawa
Toshiyuki
T
Tsunoda
D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D045325:HCT116 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; C533896:MIRN200 microRNA, human; C543800:MIRN210 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins