title: MicroRNA-187, a downstream effector of TGFβ pathway, suppresses Smad-mediated epithelial-mesenchymal transition in colorectal cancer.
abstract: Constitutive overactivation of TGFβ signaling is a common event in human cancer progression and acts as a major inducer of epithelial-mesenchymal transition (EMT). In pre-metastatic colorectal cancer (CRC) cells, however, this cascade is tightly controlled and the underlying mechanism in TGFβ stimulated hyperactivation of downstream Smad pathway remains elusive. In this study, expression of miR-187 was downregulated in colorectal cancer (CRC) compared with adjacent normal tissues. miR-187 could suppress the formation of aggressive phenotype in CRC and inactivate Smad pathway, thus preventing EMT. TGFβ stimulation significantly suppressed the expression of miR-187, and overexpressed miR-187 counteracted the influence of TGFβ on cell phenotype and downstream pathway. Furthermore, we found that miR-187 directly suppressed the expression of SOX4, NT5E and PTK6, which were identified as essential upstream effectors of Smad pathway. Together with the fact that high SOX4 or NT5E levels were associated with poor prognosis, we also demonstrated that downregulation of miR-187 was closely related to tumor metastasis and poor prognosis in CRC. These findings revealed a plausible mechanism for sustained TGFβ activation in cancer progression and might have suggested a novel miR-187-based clinical intervention target for patients with advanced CRC.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Jiaolong
authors.initials: J
authors.lastname: Shi
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yawei
authors.initials: Y
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: Yanqing
authors.initials: Y
authors.lastname: Ding
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. Electronic address: liangsmu@foxmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
mesh_terms: D015720:5'-Nucleotidase / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D058851:GPI-Linked Proteins / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D055751:SOXC Transcription Factors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000037:antagonists & inhibitors*; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D058851:GPI-Linked Proteins; C571843:MIRN187 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human; D015720:5'-Nucleotidase; C548241:NT5E protein, human
keywords: Colorectal carcinoma; Epithelial–mesenchymal transition; Transforming growth factor beta; Tumor metastasis; microRNA-187