title: Reactivation of HIC-1 gene by saRNA inhibits clonogenicity and invasiveness in breast cancer cells.
abstract: Hypermethylated in cancer 1 (HIC-1) is a tumor suppressor gene, which is epigenetically silenced in breast cancer. It is known that the loss of HIC-1, caused by promoter hypermethylation, is associated with tumor aggression and poor survival in breast carcinoma. It has been shown that small activating RNA (saRNA) targeting promoter sequences may induce gene re-expression. In the current study, saRNA was used to restore HIC-1 expression, and the effects on colony formation, invasiveness and the cell cycle in breast cancer cells were explored. dsHIC1-2998, an saRNA, exhibited activating efficacy on MCF-7 and MDA-MB-231 cancer cell lines. A clonogenicity assay showed that evident colony inhibition was induced via saRNA-mediated re-expression of HIC-1 in the two cancer cell lines. Reactivation of HIC-1 significantly inhibited cell migration and invasion, resulting in G0/G1 cell cycle arrest in these cell lines. These findings suggest that HIC-1 may be a potential target in gene therapy for the treatment of breast cancer. saRNA may function as a therapeutic option for upregulating tumor suppressor genes in breast cancer.
authors.affiliation: Department of Surgery, The Ninth People's Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Surgery, Shanghai Ruijin Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Surgery, The Ninth People's Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Surgery, The Ninth People's Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Shanyu
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Surgery, The Ninth People's Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Qiancheng
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Department of Surgery, Shanghai Ruijin Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Surgery, The Ninth People's Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
keywords: HIC-1; breast cancer; cell invasion; clonogenicity; saRNA