HRCT1, negatively regulated by miR-124-3p, promotes tumor metastasis and the growth of gastric cancer by activating the ERBB2-MAPK pathway
HRCT1, negatively regulated by miR-124-3p, promotes tumor metastasis and the growth of gastric cancer by activating the ERBB2-MAPK pathway
复制标题
HRCT1受miR-124-3p负调控，通过激活ERBB2-MAPK通路促进肿瘤转移和胃癌生长
DOI：
10.1007/s10120-022-01362-1
复制
发表时间：
2023-01-05
期刊：
影响因子：
7.4
通讯作者：
Gao, Peng
中科院分区：
文献类型：
--
作者：
Hou, Feng;Shi, Duan-Bo;Gao, Peng
背景胃癌是全球与癌症相关的死亡的第四大原因。由于肿瘤复发和转移，患者的预后很差。为了开发新的治疗策略，探索胃癌进展的机制具有重要意义。方法采用基因芯片技术对有淋巴结转移和无淋巴结转移的胃癌标本进行基因芯片检测。通过RT-qPCR对差异表达基因进行验证。免疫组织化学(IHC)法进一步检测HRCT1蛋白表达。通过体外和体内实验，研究HRCT1在肿瘤侵袭、转移和增殖中的作用。采用基因芯片、RT-qPCR和Western印迹等方法检测HRCT1下游靶基因的表达。结果HRCT1在胃癌组织中表达上调，且高表达与总生存期(OS)和无瘤生存期(DFS)有关。此外，HRCT1蛋白表达是不良OS和DFS的独立预测因子。HRCT1在体外可促进胃癌细胞的迁移、侵袭和增殖，在体内可促进肿瘤的转移和生长。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。结论HRCT1的表达上调预示着胃癌患者的预后不良。HRCT1通过激活ERBB2-MAPK通路促进肿瘤进展。受miR-124-3p负性调控的HRCT1可能成为胃癌患者潜在的治疗靶点。
BackgroundGastric 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.MethodsPrimary 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.ResultsHRCT1 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.ConclusionsThe 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.