Found programs:
Authors:Jin Yong; Du Hong; Xia Ying; Xiang Tingting; Wei Sixi; Sun Ming; Huang Hai
Keywords:gastric cancer;ABCA1;invasion;migration;epithelial-mesenchymal transition
DOI:10.19405/j.cnki.issn1000-1492.2022.11.005
〔Abstract〕 Objective To explore the effect of ATP binding cassette subfamily A member 1(ABCA1) on the invasion, migration and epithelial-mesenchymal transition(EMT) of human gastric cancer and investigate the underlying mechanism. Methods The expression of ABCA1 in human gastric cancer and its relationship with the prognosis of gastric cancer patients were analyzed by Bioinformatics analysisbased on network databases. RT-qPCR was performed to detect the expression of ABCA1 in 25 pairs of clinical gastric cancer tissue samples; RT-qPCR and Western blot were used to analyze the expression of ABCA1 in different human gastric cancer cell lines; Gene silencing technology was used to construct stable low-expressing ABCA1 gastric cancer cell line. Cell migration and invasion were determined by transwell assay; Western blot was used to detect the expression of related marker proteins in EMT and epidermal growth factor receptor(EGFR)/signal transducer and activator of transcription(STAT3) signaling pathway. Results The results of bioinformatics analysis indicated that ABCA1 was highly expressed in gastric cancer, which was positively correlated with advanced grade and stage as well as the poor prognosis of gastric cancer patients. RT-qPCR results showed that ABCA1 was highly expressed in gastric cancer tissues and gastric cancer cells HGC-27; The results of Transwell indicated that knockdown of ABCA1 could inhibit the invasion and migration of HGC-27 cells. Western blot results showed that the expression of mesenchymal cell marker proteins(Vimentin, N-Cadherin) and EMT-related transcription factors(Twist, Zeb1 and Snail) in the ABCA1 knockdown group was down-regulated, while the expression of epithelial cell marker protein E-Cadherin was up-regulated. Western blot results showed that compared with the control group, knockdown of ABCA1 inhibited the expression of EGFR downstream molecule STAT3, and reduced the phosphorylation level of EGFR and its downstream molecule STAT3. Conclusion ABCA1 is up-regulated in gastric cancer and is correlated with cell invasion, migration, EMT and indicate poor prognosis of gastric cancer patients. ABCA1 may affect the expression and activation of STAT3 by regulating EGFR, thereby inhibiting the invasion, migration and EMT of gastric cancer cells.