Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance.
BACKGROUND
MicroRNAs are endogenous small noncoding RNAs that aberrantly expressed in various carcinomas. MiR-148a and miR-152, which have the same "seed region", have not been comprehensively investigated in gastrointestinal cancers.


METHODS
Total RNA was extracted from the tissues of 101 patients with gastric cancer and 101 patients with colorectal cancer as well as their matched nontumor adjacent tissues. After polyadenylation and reverse transcription, the expression of miR-148a and miR-152 was determined using quantitative real-time polymerase chain reaction. The protein level of cholecystokinin B receptor, which might be the target gene of miR-148a and miR-152, was analyzed by Western blot in 40 patients with gastric cancer.


RESULTS
Expression levels of miR-148a and miR-152 in human gastric (p < 0.001 and p = 0.038, respectively, t-test) and colorectal (all p < 0.001) cancers were significantly lower than that in their matched nontumor adjacent tissues. Moreover, their low expression was also found in several gastrointestinal cancer cell lines compared with normal gastric epithelial cell line and normal colorectal tissue, respectively. A strong correlation was found between the expression of miR-148a and miR-152 (all p < 0.001, Pearson's correlation). Furthermore, low expression of miR-152 was correlated with increased tumor size (p = 0.023 and 0.004, respectively, Mann-Whitney U test) and advanced pT stage (p = 0.018 and 0.002, respectively) in gastrointestinal cancers. Low expression of miR-148a was also correlated with increased tumor size (p = 0.045 and 0.018, respectively) in gastrointestinal cancers, but only correlated with advanced pT stage (p = 0.023) in colorectal cancer. We also found the expression of miR-148a (p < 0.001, chi-square test) and miR-152 (p = 0.002) inversely correlated with cholecystokinin B receptor protein in gastric cancer.


CONCLUSIONS
MiR-148a and miR-152 may be involved in the carcinogenesis of gastrointestinal cancers and might be potential biomarkers in these cancers.
Chen
Yue
Y
Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Song
Yongxi
Y
Wang
Zhenning
Z
Yue
Zhenyu
Z
Xu
Huimian
H
Xing
Chengzhong
C
Liu
Zhuangkai
Z
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D026723:Polyadenylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology
D015415:Biomarkers; C550570:MIRN148 microRNA, human; C550856:MIRN152 microRNA, human; D035683:MicroRNAs