title: Epigenetic silencing of miR-181b contributes to tumorigenicity in colorectal cancer by targeting RASSF1A.
abstract: Aberrant microRNA expression is common in colorectal cancer and DNA methylation is believed to be responsible for this alteration. In this study, we performed evaluation in vivo and in vitro to determine the role of miR-181b as a potential diagnostic and prognostic biomarker in colorectal cancer. Ninety-seven pairs of colorectal cancer tissues and adjacent normal tissues were collected. The expression level and methylation status of miR-181b was determined in tissue samples and multiple colorectal cancer cell lines. RASSF1A, a predicted target gene of miR-181b, was investigated in vitro. Further mechanistic explorations were conducted. It was found that miR-181b expression was frequently downregulated in cancer samples. This lower expression level resulted from higher hypermethylation in cancer tissue and was closely related to TNM stage. Following artificial synthesis of miR-181b stimulation, colorectal cancer cell proliferation was greatly inhibited in CRC cells while apoptosis percentage markedly increased. miR-181b achieved the tumor suppressive effects via direct targeting of the RASSF1A gene. This study indicated the clinical significance of miR-181b and the influence of miR-181b promoter region in epigenetic silencing of tumorigenicity in colorectal cancer, and implied the possible usage of miR-181b as a diagnostic and prognostic biomarker in colorectal cancer.
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Lun-De
authors.initials: LD
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Zheng
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Gao-Xiang
authors.initials: GX
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Kang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Ji
authors.affiliation: Department of Medical Oncology, Jingmen Traditional Chinese Medicine Hospital, Jingmen, Hubei 448000, P.R. China.
authors.forename: Sha
authors.initials: S
authors.lastname: Hao
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D001374:Azacitidine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D001374:Azacitidine