HEAT repeat-containing protein 1 (HEATR1) is related to the progression of several cancers. However, the role of HEATR1 in gastric cancer (GC) remains unknown. In the present study, we aimed to detect the expression of HEATR1 in GC and identify its role. The expressions of HEATR1 in GC tissues were analyzed using The Cancer Genome Atlas database and by western blot analysis and immunohistochemistry. Furthermore, the HEATR1 expressions in GC cell lines MGC-803 and AGS were knocked down by using lentivirus-mediated HEATR1 shRNA. Cell proliferation and apoptosis were detected by CCK-8 and Caspase-Glo® 3/7 assays, respectively. PathScan® Signaling Antibody Array kit and Kyoto Encyclopedia of Genes and Genomes enrichment were used to study the pathways related to HEATR1. The influence of HEATR1 shRNA on the in vivo growth of GC cells was assessed by establishing a nude mouse xenograft model and conducting bioluminescence imaging. Our results showed that HEATR1 was highly expressed in GC tissues. Higher expression of HEATR1 is related to cancer progression and metastasis. Knocking down HEATR1 significantly suppressed the cell proliferation and colony formation and promoted cell apoptosis. The expression levels of phosphorylated p53, p38 MAPK, Chk2, and IKBa in shHEATR1-transfected MGC-803 cells exceeded those in shCtrl-transfected cells. HEATR1 shRNA treatment also significantly inhibited tumor growth in the mouse model. This study suggested that HEATR1 may be an oncogene and a target for GC therapy.

中文翻译：

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HEATR1在体内外促进胃癌的增殖。

含有HEAT重复序列的蛋白1（HEATR1）与几种癌症的进展有关。但是，HEATR1在胃癌（GC）中的作用仍然未知。在本研究中，我们旨在检测HEATR1在GC中的表达并确定其作用。使用The Cancer Genome Atlas数据库以及Western blot分析和免疫组化分析了HEATR1在GC组织中的表达。此外，通过使用慢病毒介导的HEATR1 shRNA敲低了GC细胞系MGC-803和AGS中的HEATR1表达。细胞增殖和凋亡分别通过CCK-8和Caspase-Glo®3/7检测来检测。使用PathScan®Signaling Antibody Array试剂盒和《京都议定书》的基因与基因组富集研究了与HEATR1相关的途径。HEATR1 shRNA对体内的影响通过建立裸鼠异种移植模型并进行生物发光成像来评估GC细胞的生长。我们的结果表明，HEATR1在GC组织中高表达。HEATR1的高表达与癌症的进展和转移有关。敲低HEATR1可显着抑制细胞增殖和集落形成并促进细胞凋亡。shHEATR1转染的MGC-803细胞中磷酸化的p53，p38 MAPK，Chk2和IKBa的表达水平超过了shCtrl转染的细胞。HEATR1 shRNA处理还显着抑制了小鼠模型中的肿瘤生长。这项研究表明，HEATR1可能是癌基因和GC治疗的靶标。