title: Suppression of KLF8 induces cell differentiation and sensitizes colorectal cancer to 5-fluorouracil.
abstract: KLF8 is a member of the KLF transcription factor family that plays an important role in oncogenesis. However, the role of KLF8 in colorectal cancer remains unknown. The aims of the present study were to examine KLF8 expression in colorectal cancers, to determine the role of KLF8 in cell differentiation and to investigate the antiproliferative effect of KLF8 silencing. The expression of KLF8 and phospho-ERK proteins was analyzed, and the effects of KLF8 suppression on cell differentiation and growth were evaluated. In addition, the biological impact of KLF8 knockdown on colorectal cancer cells was investigated in vitro and in vivo. The expression of the KLF8 protein was higher in 10/14 (71.43%) fresh cancer tissues compared with adjacent normal tissues, and the blockade of ERK signaling by U0126 decreased the expression of KLF8 in a time- and dose-dependent manner. Furthermore, KLF8-siRNA induced the expression of carcinoembryonic antigen (CEA) and E-cadherin as well as the maturation of F-actin. KLF8 suppression inhibited serum-dependent, anchorage‑dependent and -independent cell growth. Moreover, KLF8 silencing induced apoptosis and sensitized cancer cells to 5-fluorouracil (5-FU). A strong antitumorigenic effect by lenti-KLF8-shRNA, which was enhanced when combined with 5-FU treatment, was exerted in nude mice. Thus, KLF8 suppression induced cell differentiation and inhibited tumorigenesis.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Oncology, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang, Henan, P.R. China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Luo
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Mengnan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Cunlong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Chudi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Side
authors.initials: S
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jide
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C507402:KLF8 protein, human; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D005472:Fluorouracil