Interaction between ACOT7 and LncRNA NMRAL2P via Methylation Regulates Gastric Cancer Progression
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Purpose: Gastric cancer (GC) has a very poor prognosis when diagnosed at a late stage. Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the acyl coenzyme family that catalyzes the hydrolysis of fatty acyl-CoAs into unesterified free fatty acid and coenzyme A. The purpose of this study was to investigate the expression levels of ACOT7 in GC and mechanisms related therewith. Materials and Methods: Screening of systematic biology studies revealed ACOT7 as a key gene in GC, as well as involvement of the long non-coding RNA NMRAL2P in ACOT7 expression. In this study, GC tissues and adjacent tissue samples were obtained from 10 GC patients at the Department of Gastrointestinal Surgery. GES1 and SGC-7901 cells were collected and treated to silence ACOT7 and overexpress NMRAL2P. The expressions of ACOT7 and NMRAL2P were detected by real-time quantitative PCR and Western blot. Additionally, cell proliferation, apoptosis, migration, and invasion were examined. Results: ACOT7 was upregulated in gastric tumor tissues and GC cell lines. ACOT7 gene silencing induced a less malignant phenotype and was closely correlated to reduced cell proliferation and migration, altered cell cycle, and increased apoptosis. Furthermore, NMRAL2P was downregulated in tumor tissues and GC cell lines. NMRAL2P overexpression induced a more malignant phenotype and significantly inhibited the expression of ACOT7. Importantly, NMRAL2P indirectly methylated ACOT7 by binding to DNMT3b, thereby suppressing ACOT7 expression. Conclusion: NMRAL2P activation suppresses ACOT7 expression in GC. Thus, ACOT7 could be a promising target for the treatment of GC.
Abstract
Purpose: Gastric cancer (GC) has a very poor prognosis when diagnosed at a late stage. Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the acyl coenzyme family that catalyzes the hydrolysis of fatty acyl-CoAs into unesterified free fatty acid and coenzyme A. The purpose of this study was to investigate the expression levels of ACOT7 in GC and mechanisms related therewith. Materials and Methods: Screening of systematic biology studies revealed ACOT7 as a key gene in GC, as well as involvement of the long non-coding RNA NMRAL2P in ACOT7 expression. In this study, GC tissues and adjacent tissue samples were obtained from 10 GC patients at the Department of Gastrointestinal Surgery. GES1 and SGC-7901 cells were collected and treated to silence ACOT7 and overexpress NMRAL2P. The expressions of ACOT7 and NMRAL2P were detected by real-time quantitative PCR and Western blot. Additionally, cell proliferation, apoptosis, migration, and invasion were examined. Results: ACOT7 was upregulated in gastric tumor tissues and GC cell lines. ACOT7 gene silencing induced a less malignant phenotype and was closely correlated to reduced cell proliferation and migration, altered cell cycle, and increased apoptosis. Furthermore, NMRAL2P was downregulated in tumor tissues and GC cell lines. NMRAL2P overexpression induced a more malignant phenotype and significantly inhibited the expression of ACOT7. Importantly, NMRAL2P indirectly methylated ACOT7 by binding to DNMT3b, thereby suppressing ACOT7 expression. Conclusion: NMRAL2P activation suppresses ACOT7 expression in GC. Thus, ACOT7 could be a promising target for the treatment of GC.
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