Toll-like receptor 4 small interfering RNA inhibits proliferation, invasion and migration in colorectal cancer cells by downregulating acyl coenzyme A cholesterol acyltransferase 1 expression

Abstract

Objective Toll-like receptor 4 (TLR4) is involved in tumor development. Numerous studies have confirmed that TLR4 mediates processes in tumorigenesis, for example, inflammation, proliferation and invasion. However, the effects of TLR4 on colorectal cancer development have not been fully elucidated. The present study aimed to evaluate the effects and mechanisms of TLR4 on colorectal cancer development. Methods The expression of TLR4 and acyl coenzyme A cholesterol acyltransferase 1 (ACAT1) in colorectal cancer tissues and cell lines was detected using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Cell counting kit-8 (CCK-8) and Transwell assays were used to evaluate the effects of TLR4 silencing on cell proliferation, migration and invasion in HT29 and SW480. RT-PCR and Western blotting were used to determine the regulation between TLR4 and ACAT1. Results Both TLR4 and ACAT1 were highly expressed in colorectal cancer tissues (TLR4 mRNA: 2.395 0±0.247 7 and 1.093 0±0.075 8, P=0.000; ACAT1 mRNA: 2.196 0±0.189 5 and 1.093 0±0.075 8, P=0.000) and cell lines. Inhibition of TLR4 suppressed cell proliferation, migration and invasion in HT29 and SW480. TLR4 small interfering RNA(siRNA) decreased ACAT1 expression in HT29 (mRNA: 0.350 0±0.145 7 and 1.017 0±0.145 0, P=0.032; Protein: 0.523 3±0.052 1 and 1.140 0±0.105 8, P=0.006), and that overexpression of ACAT1 by pLV-Neo-ACAT1 abolished the effects of TLR4 siRNA on colorectal cancer cell lines. Conclusion TLR4 siRNA inhibits cell proliferation, migration and invasion by suppressing ACAT1 expression, suggesting that TLR4 may be a potential therapeutic target for the treatment of colorectal cancer. Key words: Toll-like receptor 4; Small interfering RNA; Colorectal cancer; Acyl coenzyme A cholesterol acyltransferase 1