title: Elevated microRNA-31 expression regulates colorectal cancer progression by repressing its target gene SATB2.
abstract: Several studies have brought about increasing evidence to support the hypothesis that miRNAs play a pivotal role in multiple processes of carcinogenesis, including cell growth, apoptosis, differentiation, and metastasis. In this study, we investigated the potential role of miR-31 in colorectal cancer (CRC) aggressiveness and its underlying mechanisms. We found that miR-31 increased in CRC cells originated from metastatic foci and human primary CRC tissues with lymph node metastases. Furthermore, the high-level expression of miR-31 was significantly associated with a more aggressive and poor prognostic phenotype of patients with CRC (p < 0.05). The stable over-expression of miR-31 in CRC cells was sufficient to promote cell proliferation, invasion, and migration in vitro. It facilitated tumor growth and metastasis in vivo too. Further studies showed that miR-31 can directly bind to the 3'untranslated region (3'UTR) of SATB2 mRNA and subsequently repress both the mRNA and protein expressions of SATB2. Ectopic expression of SATB2 by transiently transfected with pCAG-SATB2 vector encoding the entire SATB2 coding sequence could reverse the effects of miR-31 on CRC tumorigenesis and progression. In addition, ectopic over-expression of miR-31 in CRC cells induced epithelial-mesenchymal transition (EMT). Our results illustrated that the up-regulation of miR-31 played an important role in CRC cell proliferation, invasion, and metastasis in vitro and in vivo through direct repressing SATB2, suggesting a potential application of miR-31 in prognosis prediction and therapeutic application in CRC.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China ; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China ; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Health Science Center, Peking University, Beijing, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China ; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China ; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Ding
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C534612:MIRN31 microRNA, human; D036961:Matrix Attachment Region Binding Proteins; D035683:MicroRNAs; D012334:RNA, Neoplasm; C521297:SATB2 protein, human; D014157:Transcription Factors