title: TUC.338 promotes invasion and metastasis in colorectal cancer.
abstract: Ultraconserved regions (UCRs) are non-protein coding gene sequences that are strictly conserved across among different species. Emerging evidence demonstrates that transcribed ultraconserved regions (TUCRs) encoding noncoding RNAs serve as regulators of gene expression. In recent decades, increasing evidence implicates the involvement of UCRs in carcinogenesis. The role of TUC.338 in cervical cancers was an oncogene in previous studies. Until now, the role of TUC.338 in colorectal cancers remains undefined. This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis. Transfection with small interfering RNA (siRNA) markedly inhibited cell migration and invasion in SW480 and HCT116 colorectal cancer cell lines. TIMP-1 was demonstrated to be negatively regulated by TUC.338 at the posttranscriptional level, via a specific target site within the 3' untranslated region by dual-luciferase reporter assay. The expression of TIMP-1 was also observed to inversely correlate with TUC.338 expression in CRC tissues. Over-expression of TIMP-1 with migRI-TIMP-1-GFP inhibited CRC cell migration and invasion and down-regulates MMP9, resembling that of TUC.338-siRNA. Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion.
authors.affiliation: Department of Pathology, The Second Clinical Medical College, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou, China.|Department of Pathology, The First People's Hospital of Yangzhou, 368 Hanjiang Middle Road, Yangzhou, China.|Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou University, 11 Huaihai Road, Yangzhou, China.
authors.forename: Chenghai
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, The First People's Hospital of Yangzhou, 368 Hanjiang Middle Road, Yangzhou, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, The First People's Hospital of Yangzhou, 368 Hanjiang Middle Road, Yangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pathology, The First People's Hospital of Yangzhou, 368 Hanjiang Middle Road, Yangzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pathology, The First People's Hospital of Yangzhou, 368 Hanjiang Middle Road, Yangzhou, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Pathology, The First People's Hospital of Yangzhou, 368 Hanjiang Middle Road, Yangzhou, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pathology, The Second Clinical Medical College, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou, China.|Department of Pathology, The First People's Hospital of Yangzhou, 368 Hanjiang Middle Road, Yangzhou, China.
authors.forename: Yongling
authors.initials: Y
authors.lastname: Ding
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D017124:Conserved Sequence / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009857:Oncogenes; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C000615821:long non-coding RNA TUC338, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: MMP9; TIMP-1; TUC.338; colorectal carcinoma; metastasis