title: Downregulation of miR-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth.
abstract: Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. It has been demonstrated that COX-2 overexpression depends on different cellular pathways, involving both transcriptional and post-transcriptional regulation. MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators. Here, we characterize miR-101 expression and its role in the regulation of COX-2 expression, which in turn, will provide us with additional insights into the potential therapeutic benefits of exogenous miR-101 for treatment of gastric cancer. Our results showed that miR-101 levels in gastric cancer tissues were significantly lower than those in the matched normal tissue (P < 0.01). Furthermore, lower levels of miR-101 were associated with increased tumor invasion and lymph node metastasis (P < 0.05). We also found an inverse correlation between miR-101 and COX-2 expression in both gastric cancer specimens and cell lines. Significant decreases in COX-2 mRNA and COX-2 levels were observed in the pre-miR-101-infected gastric cancer cells. One possible mechanism of interaction is that miR-101 inhibited COX-2 expression by directly binding to the 3'-UTR of COX-2 mRNA. Overexpression of miR-101 in gastric cancer cell lines also inhibited cell proliferation and induced apoptosis in vitro, as well as inhibiting tumor growth in vivo. These results collectively indicate that miR-101 may function as a tumor suppressor in gastric cancer, with COX-2 as a direct target.
authors.affiliation: Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Xiao-Pu
authors.initials: XP
authors.lastname: He
authors.forename: Yun
authors.initials: Y
authors.lastname: Shao
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Chen
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Sun
authors.forename: Hai-Chen
authors.initials: HC
authors.lastname: Xu
authors.forename: Xian
authors.initials: X
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Tang
authors.forename: Xi-Feng
authors.initials: XF
authors.lastname: Zheng
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Xue
authors.forename: Guo-Chang
authors.initials: GC
authors.lastname: Huang
authors.forename: Wei-Hao
authors.initials: WH
authors.lastname: Sun
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D020413:3' Untranslated Regions; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human