文献类型：期刊文献

英文题名：Silencing of COPB2 inhibits the proliferation of gastric cancer cells and induces apoptosis via suppression of the RTK signaling pathway

作者：An, Caixia[1,2];Li, Hailong[3,4];Zhang, Xueyan[3,4];Wang, Jing[3,4];Qiang, Yi[5];Ye, Xinhua[6];Li, Qiang[7];Guan, Quanlin[8];Zhou, Yongning[1,2]

第一作者：An, Caixia

通信作者：Zhou, YN[1]

机构：[1]Lanzhou Univ, Hosp 1, Dept Gastroenterol, 1 West Donggang Rd, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Univ, Key Lab Gastrointestinal Dis Gansu Prov, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Sch Clin Med, Dept Clin Lab Diag, Lanzhou 730000, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Key Lab Tradit Chinese Herbs & Prescript Innovat, Lanzhou 730000, Gansu, Peoples R China;[5]Gansu Prov Maternal & Child Hlth Hosp, Div Cardiac Surg, Lanzhou 730050, Gansu, Peoples R China;[6]Lanzhou Univ, Hosp 1, Dept Pediat, Lanzhou 730000, Gansu, Peoples R China;[7]Lanzhou Univ, Hosp 2, Div Neurosurg, Lanzhou 730000, Gansu, Peoples R China;[8]Lanzhou Univ, Hosp 1, Dept Surg Oncol, Lanzhou 730000, Gansu, Peoples R China

第一机构：Lanzhou Univ, Hosp 1, Dept Gastroenterol, 1 West Donggang Rd, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Hosp 1, Dept Gastroenterol, 1 West Donggang Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2019

卷号：54

期号：4

起止页码：1195

外文期刊名：INTERNATIONAL JOURNAL OF ONCOLOGY

收录：;Scopus(收录号：2-s2.0-85062656460);WOS:【SCI-EXPANDED(收录号:WOS:000461097600005)】；

基金：This study was supported by the Lanzhou Science and Technology Planning Project (grant no. 2016-3-113), the 60th Project of China Postdoctoral Foundation (grant no. 2016M602888), the China's National Science and Technology Program for Public Wellbeing (grant no. 2012GS620101) and the National Key Research and Development Plan (grant no. 2017YFC0908302).

语种：英文

外文关键词：coatomer protein complex subunit beta 2; gastric cancer; apoptosis; receptor tyrosine kinase signaling pathway

摘要：Emerging studies have reported that coatomer protein complex subunit beta 2 (COPB2) is overexpressed in several types of malignant tumor; however, to the best of our knowledge, no studies regarding COPB2 in gastric cancer have been published thus far. Therefore, the present study aimed to determine the significance and function of COPB2 in gastric cancer. COPB2 expression in gastric cancer cell lines was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. In addition, lentivirus-short hairpin RNA (shRNA) COPB2 (Lv-shCOPB2) was generated and used to infect BGC-823 cells to analyze the effects of COPB2 on the cancerous phenotype. The effects of shRNA-mediated COPB2 knockdown on cell proliferation were detected using MTT, 5-bromo-2-deoxyuridine and colony formation assays. In addition, the effects of COPB2 knockdown on apoptosis were analyzed by flow cytometry. Nude mice and fluorescence imaging were used to characterize the regulation of tumor growth in vivo, and qPCR and immunohistochemistry were subsequently conducted to analyze COPB2 expression in xenograft tumor tissues. Furthermore, a receptor tyrosine kinase (RTK) signaling pathway antibody array was used to explore the relevant molecular mechanisms underlying the effects of COPB2 knockdown. The results revealed that COPB2 mRNA was abundantly overexpressed in gastric cancer cell lines, whereas knockdown of COPB2 significantly inhibited cell growth and colony formation ability, and led to increased cell apoptosis in vitro. The tumorigenicity assay revealed that knockdown of COPB2 reduced tumor growth in nude mice, and fluorescence imaging indicated that the total radiant efficiency of mice in the Lv-shCOPB2-infected group was markedly reduced compared with the mice in the Lv-shRNA control-infected group in vivo. The antibody array assay revealed that the levels of phosphorylation in 23 target RTKs were significantly reduced: In conclusion, COPB2 was highly expressed in gastric cancer cell lines, and knockdown suppressed colony formation and promoted cell apoptosis via inhibiting the RTK signaling and its downstream signaling cascade molecules. Therefore, COPB2 may present a valuable target for gene silencing strategy in gastric cancer.