title: Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2.
abstract: The aberrant expression of microRNAs (miRNAs) is associated with colorectal carcinogenesis, but the underlying mechanisms are not clear. This study showed that the miRNA-27a (miR-27a) was significantly reduced in colorectal cancer tissues and colorectal cancer cell lines, and that the reduced miR-27a was associated with distant metastasis and colorectal cancer clinical pathological stages-miR-27a was lower at stages III/IV than that at stage II. Bioinformatic and systemic biological analysis predicted several targets of miR-27a, among them SGPP1 and Smad2 were significantly affected. SGPP1 and Smad2 at mRNA and protein levels were negatively correlated with miR-27a in human colorectal cancer tissues and cancer cell lines. Increased miR-27a significantly repressed SGPP1 and Smad2 at transcriptional and translational levels. Functional studies showed that increasing miR-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-STAT3 and upregulation of cleaved caspase 3. In vivo, miR-27a inhibited colon cancer cell growth in tumor-bearing mice. Taken together, this study has revealed miR-27a as a tumor suppressor and has identified SGPP1 and Smad2 as novel targets of miR-27a, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in colorectal cancer. Therefore, miR-27a could be a useful biomarker for monitoring colorectal cancer development and progression, and also could have a therapeutic potential by targeting SGPP1, Smad2 and STAT3 for colorectal cancer therapy.
authors.affiliation: Department of Immunology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
authors.forename: Yongchen
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Surgery, the First Affiliated Hospital, Xinxiang Medical University, Weihui, China.
authors.forename: Zexin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Xinxiang Central Hospital, Xinxiang Medical University, Xinxiang, China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Surgery, the First Affiliated Hospital, Xinxiang Medical University, Weihui, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Immunology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, China; Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, China; Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019295:Computational Biology / Q000379:methods; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D051899:Smad2 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C531388:MIRN27 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C497782:SMAD2 protein, human; D051899:Smad2 Protein; C498527:SGPP1 protein, human; D010744:Phosphoric Monoester Hydrolases