title: Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent.
abstract: microRNA regulation network is important for the cancer genetic heterogeneity. Relative to the increasing numbers of microRNA's targets identified, upstream regulatory mechanisms that control functional microRNAs are less well-documented. Here, we investigated the function of miR-31, a pleiotropically-acting microRNA, in esophageal squamous cell cancer (ESCC). We demonstrated that miR-31 only exerted tumor-suppressive effects in TE-7 ESCC cells, but not in TE-1 ESCC cells, although both of these cell lines harbor inactive p53. Interestingly, TE-1 cells highly expressed p21, while p21 levels were virtually undetectable in TE-7 cells, suggesting a p21-dependent mechanism of miR-31-mediated tumor suppression. Accordingly, knockdown of p21 in TE-1 cells reversed the tumor suppressive actions of miR-31. In patient ESCC specimens, real-time RT-PCR analysis revealed that expression of E2F2 and STK40, two known miR-31 target oncogenes, was negatively correlated with the expression of miR-31 in a p21-dependent manner, supporting the conclusion that miR-31 only downregulates its target oncogenes when p21 levels are low. Collectively, these data suggest a novel mechanism through which the tumor-suppressive effect of miR-31 is p21-dependent. In addition, we speculate that delivery of miR-31 could provide therapeutic benefit in the personalized management of a subgroup of ESCC patients with p21-deficient tumors.
authors.affiliation: Laboratory for Translational Oncology basic medicine college, Hubei University of Science and Technology, Xianning, Hubei province, China ; Department of Biotherapy and Gastrointestinal Medical Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China ; Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, the Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Biotherapy and Gastrointestinal Medical Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China ; Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Biotherapy and Gastrointestinal Medical Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China ; Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Gefei
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, the Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, the Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Shaobin
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Guanwu
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
authors.affiliation: Department of Biotherapy and Gastrointestinal Medical Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China ; Tumor Tissue Bank, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China ; Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
keywords: esophageal squamous cell cancer; miR-31; microRNA; p21; personalized medicine