title: MicroRNA-135b regulates metastasis suppressor 1 expression and promotes migration and invasion in colorectal cancer.
abstract: MicroRNAs (miRNAs, miRs) play important roles in pathogenesis and development of human diseases, including malignancy. Some may affect tumor progression through targeting tumor suppressor genes. MiR-135b has been shown to be upregulated in CRC. In this study, we evaluated the role of miR-135b in colorectal cancer (CRC) and its regulatory role for metastasis suppressor-1 (MTSS1) and its mechanisms. The levels of miR-135b and MTSS1 gene expression in 35 CRC and corresponding cancer-adjacent tissues, 27 colorectal adenoma, and 16 normal tissue samples were quantified using qRT-PCR and western blot analysis. The effect of miR-135b on MTSS1 expression was assessed by miR-135b mimics or inhibitor transfection to deregulate miR-135b expression. The direct interaction between them was verified by 3'-UTR dual-luciferase reporter assay. Furthermore, the roles of miR-135b in regulating CRC cells migration and invasion properties were analyzed with miR-135b mimics or inhibitor-transfected cells and silenced expression of MTSS1 in miR-135b inhibitor transfected cells. CRC tissues showed significantly upregulated miR-135b expression and reduced MTSS1 expression. High miR-135b levels were significantly associated with lymph node and distant metastasis. The miR-135b inhibitor decreased miR-135b expression and caused MTSS1 upregulation at the post-transcriptional level. However, overexpression of miR-135b caused MTSS1 protein downregulation. The 3'-UTR of MTSS1 harbored a binding site for miR-135b. Finally, miR-135b inhibitor-transfected cells exhibited markedly reduced cell migration and invasive abilities, and this effect could be reversed by MTSS1-siRNA. Our results demonstrated that miR-135b downregulated MTSS1 expression and contributed to CRC cell invasion, indicating its involvement in CRC progression.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, South Peoples Avenue No. 57, Xiashan District, Zhanjiang, Guangdong, China, winnie556644@163.com.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Wu
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Wang
authors.forename: Pengchun
authors.initials: P
authors.lastname: Yang
authors.forename: Jingfang
authors.initials: J
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Guoli
authors.initials: G
authors.lastname: Wei
authors.forename: Shicai
authors.initials: S
authors.lastname: Ye
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C544965:MIRN135 microRNA, human; C486778:MTSS1 protein, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering