xenograft tumor model was introduced to investigate the role of OLA1 in vivo. Results OLA1 demonstrated a higher expression in gastric cancer tissues with stage III-IV compared to paired normal tissue (25 paired sample; P<0.001), and the high level of OLA1 was correlated with poor prognosis (HR=2.40, P=0.008) and decreased sensitivity to 5-fluorouracil adjuvant chemotherapy (HR=2.63, P<0.001). Overexpression of OLA1 in gastric cancer cells reduced the sensitivity to 5-fluorouracil treatment, while knockdown of OLA1 by shRNA in gastric cancer cells significantly inhibited the cell proliferation, migration, invasion and tumorigenicity. However, OLA1 did not affect the cell cycle and proliferation in normal gastric epithelium cells. Mechanistically, WGCNA analysis of TCGA RNA-seq data suggested that high expression of OLA1 will promote G2/M phase transition and eventually lead to tumor progression, while knockdown of OLA1 in gastric cancer cells significantly prolonged G2/M phase (control vs KD: 10.65% vs 21.59%; P<0.01). Conclusions OLA1 inhibition could suppress gastric cancer progression and enhance the sensitivity to adjuvant chemotherapy with sparing normal gastric epithelium cells. Therefore, OLA1 could be a novel and promising target in treating gastric cancer.
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