title: SP1-mediated microRNA-520d-5p suppresses tumor growth and metastasis in colorectal cancer by targeting CTHRC1.
abstract: Recent evidence suggests that miR-520 family has an important role in regulating tumorigenesis and development of various types of solid cancers. However, as one of the most common cancers in the world, there is little known about the underlying regulatory mechanisms of miR-520 in colorectal cancer (CRC). In the present study, we investigated the expression of microRNA-520d-5p (miR-520d-5p) in CRC specimens and then explored its potential role and mechanism in CRC progression. We found that miR-520d-5p was markedly down-regulated in CRC clinical specimens compared with adjacent normal tissues by real-time PCR. Dual-luciferase assays confirmed that miR-520d-5p directly targeting CTHRC1 and SP1 transactivate miR-520d-5p by binding to its upstream promoter region. The biological functional experiments showed that ectopic re-expression of miR-520d-5p suppressed CRC cell proliferation, migration and invasion, whereas the inhibition of miR-520d-5p displayed an inverse effect in vitro and in vivo. Western blot shown that miR-520d-5p abrogated the epithelial-mesenchymal transition by inactivating the phosphorylation of Erk1/2. In conclusion, our findings indicate that miR-520d-5p is significantly down-expressed and involved in CRC progression and metastasis by targeting CTHRC1 and regulated by SP1, which provide new support for miR-520d-5p maybe as a novel anti-onco molecular target for the treatment of CRC in the future.
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University No.1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University No.1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Minimally Invasive Gastrointestinal Surgery, Beijing Cancer Hospital and Institute, Peking University Cancer Hospital, Peking University School of Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Beijing 100142, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tan
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University No.1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, China.
authors.forename: Geng-Tai
authors.initials: GT
authors.lastname: Ye
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University No.1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University No.1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University No.1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University No.1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, China.
authors.forename: Jie-Fu
authors.initials: JF
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University No.1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, China.
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University No.1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, China.
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Li
keywords: CTHRC1; Colorectal cancer; EMT; SP1; microRNA-520d-5p; p-Erk1/2