Silencing of COL1A2, COL6A3, and THBS2 inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3k‐Akt signaling pathway

• Published in: Journal of cellular biochemistry Vol. 119; no. 6; pp. 4420 - 4434
• Main Authors: Ao, Ran, Guan, Lin, Wang, Ying, Wang, Jia‐Ni
• Format: Journal Article
• Language: English
• Published: United States 01.06.2018
• Subjects: apoptosis; COL1A2; COL6A3; gastric cancer cells; gene silencing; invasion; migration; PI3K‐Akt signaling pathway; proliferation; THBS2; gastric cancer cells; PI3K-Akt signaling pathway; COL1A2; invasion; proliferation; gene silencing; migration; COL6A3; apoptosis; THBS2
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.26524

This study explores the effect of COL1A2, COL6A3, and THBS2 gene silencing on proliferation, migration, invasion, and apoptosis of gastric cancer cells through the PI3K‐Akt signaling pathway. The gastric cancer microarray expression data (GSE19826, GSE79973, and GSE65801) was analyzed. Gastric cancer tissues and corresponding adjacent normal tissues were extracted from patients. Positive expression rate of PI3K, Akt, and p‐Akt was measured with immunohistochemistry. Two cell lines, BGC‐823 and SGC‐7901, were transfected and cells were grouped into blank, negative control, COL1A2‐shRNA, COL6A3‐shRNA, and THBS2‐shRNA groups. Expressions of COL1A2, COL6A3, and THBS2 in gastric cancer cells transfected with corresponding silencing sequences were evaluated by RT‐qPCR and Western blot. MTT assay, Transwell, and cell scratch tests were conducted to evaluate cell proliferation, invasion, and migration capacity, respectively. Flow cytometry was used to evaluate cell cycle distribution and apoptosis. The positive expression of PI3K, Akt, and p‐Akt was higher in gastric cancer tissues compared with adjacent normal tissues, and the mRNA expression of COL1A2, COL6A3, and THBS2 was increased in gastric cancer tissues. Akt, p‐Akt, and PI3K expression drastically decreased in cells transfected with COL1A2, COL6A3, and THBS2 silencing sequences. Cells transfected with COL1A2, COL6A3, and THBS2 silencing sequences exhibited promoted apoptosis but inhibited proliferation, migration, and invasion. This study demonstrates that COL1A2, COL6A3, and THBS2 gene silencing inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3K‐Akt signaling pathway. COL1A2, COL6A3, and THBS2 gene silencing inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3K‐Akt signaling pathway.