title: Targeting Six1 by lentivirus-mediated RNA interference inhibits colorectal cancer cell growth and invasion.
abstract: The Six1 homeodomain protein is a developmental transcription factor that has been implicated in tumor onset and progression. Recently, it's reported that overexpression of Six1 is sufficient to induce epithelial-to-mesenchymal transition (EMT) and metastasis of colorectal cancer. Moreover, its expression is significantly associated with poorer overall survival probability in advanced-stage colorectal cancer. To address whether Six1 could serve as a therapeutic target for human colorectal cancer, we used a lentivirus-mediated short hairpin RNA (shRNA) gene knockdown method to suppress the expression of Six1 in colorectal cancer cells. We showed that lentivirusmediated shRNA targeted to Six1 gene efficiently reduced its expression in colorectal cancer cells at both mRNA and protein levels. In vitro functional assays revealed that knockdown of Six1 significantly suppressed cell proliferation, and inhibited cell migration and invasion of colorectal cancer cells. Furthermore, tumor xenograft model demonstrated that downregulation of Six1 dramatically inhibited colorectal cancer growth in vivo. In conclusion, these findings suggest that lentivirus-mediated Six1 inhibition may represent a novel therapeutic approach for treatment of colorectal cancer.
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Nan
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Zhenchang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Surgery, People's Hospital of Henan Province Zhengzhou 450003, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D045325:HCT116 Cells; D019073:HT29 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D018398:Homeodomain Proteins; C099236:SIX1 protein, human
keywords: Six1; cell growth; colorectal cancer; invasion