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: Xinpeng Shi, Xiaoyong Luo, Qingqing Yan, Wenjing Zhang, Yao Wu, Mengnan Zhang, Jinjun Zhao, Ying Peng, Ye Chen, Yali Zhang, Cunlong Chen, Tianming Cheng, Chudi Chen, Side Liu, Yang Bai, Jide Wang
• Journal: Oncology reports (Oncol Rep) Vol. 34 Issue 3 Pg. 1221-30 (Sep 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 26133391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• KLF8 protein, human
• Kruppel-Like Transcription Factors
• RNA, Small Interfering
• Repressor Proteins
• Fluorouracil

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis
• Blotting, Western
• Cell Differentiation (genetics)
• Cell Transformation, Neoplastic (genetics)
• Colorectal Neoplasms (pathology)
• Drug Resistance, Neoplasm (genetics)
• Fluorescent Antibody Technique
• Fluorouracil (pharmacology)
• Gene Expression Regulation, Neoplastic
• Humans
• Kruppel-Like Transcription Factors
• Mice
• Mice, Nude
• RNA, Small Interfering
• Repressor Proteins (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection
• Xenograft Model Antitumor Assays