胃癌是全球死于癌症的第四大原因。肿瘤复发和转移的影响使患者预后不佳。为了开发新的治疗策略，探究胃癌进展的机制非常重要。将具有淋巴结转移（LNM）和没有LNM的原发性胃癌样本进行了mRNA微阵列试验，通过RT-qPCR验证差异表达基因。使用免疫组化（IHC）检测了HRCT1蛋白表达情况。进行了体外和体内试验以研究HRCT1在肿瘤侵袭，转移和增殖中的作用。通过微阵列，RT-qPCR和Western blot检测了HRCT1下游靶基因的表达。进行了双荧光素酶记者和Western blot试验以确定miRNAs靶向HRCT1。HRCT1在胃癌中上调表达，高HRCT1表达与差的总体生存（OS）和无病生存（DFS）相关。此外，HRCT1蛋白表达是差OS和DFS的独立预测因子。HRCT1可促进胃癌细胞在体外的迁移，侵袭和增殖以及肿瘤转移和生长。值得注意的是，我们的数据显示HRCT1通过激活ERBB2-MAPK信号通路促进胃癌进展。至少部分地，HRCT1的表达可以被miR-124-3p负调节。HRCT1的上调表达预示着胃癌患者预后不佳。HRCT1通过激活ERBB2-MAPK通路促进肿瘤进展。HRCT1受miR-124-3p负调控，可能是胃癌患者的潜在治疗靶点。©2023年。作者通过独家许可授权国际胃癌协会和日本胃癌协会。

Gastric cancer is the fourth leading cause of cancer-related deaths worldwide. And patient outcomes are poor due to tumor relapse and metastasis. To develop new therapeutic strategies, it is of great importance to explore the mechanism underlying the progression of gastric cancer.Primary gastric cancer samples with lymph node metastases (LNM) and without LNM were subjected to mRNA microarray assay. The differentially expressed genes were confirmed by RT-qPCR. HRCT1 protein expression was further detected using an immunohistochemistry (IHC) assay. In vitro and in vivo assays were performed to investigate the role of HRCT1 in tumor invasion, metastasis, and proliferation. The expressions of the downstream target genes of HRCT1 were detected by microarray, RT-qPCR and Western blot assays. Dual-luciferase reporter and Western blot assays were carried out to identify miRNAs target to HRCT1.HRCT1 was upregulated in gastric cancer, and high expression of HRCT1 was associated with poor overall survival (OS) and disease-free survival (DFS). Moreover, HRCT1protein expression was an independent predictor for poor OS and DFS. HRCT1 could promote gastric cancer cells' migration, invasion, and proliferation in vitro as well as tumor metastasis and growth in vivo. Notably, our data showed that HRCT1 promoted gastric cancer progression by activating the ERBB2-MAPK signaling pathway. At least partially, the expression of HRCT1 could be negatively regulated by miR-124-3p.The upregulated expression of HRCT1 predicts poor survival for patients with gastric cancer. HRCT1 promotes tumor progression by activating the ERBB2-MAPK pathway. HRCT1, negatively regulated by miR-124-3p, may be a potential therapeutic target for patients with gastric cancer.© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.