Decreased expression of microRNA-143 and -145 in human gastric cancers.
OBJECTIVE
Downregulation of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. We investigated the role of the miRNAs miR-143 and miR-145 in gastric cancers.


METHODS
The expression levels of miR-143 and miR-145 in the samples from 43 patients with gastric cancer were determined by real-time PCR using TaqMan assay. The growth inhibitory effect was estimated by the transfection of human gastric cancer cells with the miRNA.


RESULTS
The expression levels of miR-143 and -145 were decreased in most human gastric cancers examined, as previously reported to occur in colon tumors. The transfection of human gastric MKN-1 cells with miR-145 resulted in a greater growth inhibitory effect than that with miR-143, results which were contrary to those in colon cancers. In MKN-1 cells, an additive effect on growth inhibition was shown by the combined transfection with miR-143 and miR-145; further, higher sensitivity to 5-fluorouracil was also observed following the transfection with miR-143 or miR-145. The possible candidate target messenger RNAs of miR-145 were identified to be insulin receptor substrate-1 and beta-actin.


CONCLUSIONS
Taken together, these findings suggest that miR-143 and miR-145 act as anti-oncomirs common to gastrointestinal tumors.
Department of Medical Oncology, Gifu International Institute of Biotechnology, Kakamigahara, Japan.
Takeshi
T
Takagi
Akio
A
Iio
Yoshihito
Y
Nakagawa
Tomoki
T
Naoe
Nobuhiko
N
Tanigawa
Yukihiro
Y
Akao
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D005472:Fluorouracil