Qu Ye-Min, Chen Ai, Zhao Xue, Wang Zan, Guo Dong, Shao Shu-Li, Tao Yuan-Yong, Li Qiu-Jing, Wang Ming-Yi, Ma Wan-Shan
Department of Clinical Laboratory Medicine, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, 250014, Shandong, People's Republic of China.
Department of Central Lab, Weihai Municipal Hospital, Shandong University, Weihai, 264200, Shandong, People's Republic of China.
Mol Biol Rep. 2023 Feb;50(2):1517-1531. doi: 10.1007/s11033-022-08090-w. Epub 2022 Dec 13.
Gastric cancer is heterogeneous cancer and the causes of this disease are complex. New diagnostic and therapeutic targets are urgently needed to explore. Huntingtin-associated protein 1 (HAP1) is directly related to Huntington's disease (HD). However, patients with Huntington's disease have a lower incidence of cancer. Therefore, we are committed to studying the correlation between HAP1 and gastric carcinogenesis and development.
Immunohistochemical staining, western blot analysis, and RT-qPCR were conducted to explore the localization and expression of HAP1 in gastric cancer. To study the biological significance of HAP1, we overexpressed HAP1 in both MKN28 and AGS cell lines by lentivirus infection. To explore the role of HAP1 in cell proliferation, the cells counting assay, EdU incorporation assay, and colony formation assay were carried out. We performed the wound healing assay and transwell assay to study the cell migration and invasion. To further investigate whether HAP1 could regulate gastric cancer cell death during glucose deprivation, Annexin V-FITC/PI staining was performed. In our study, we elucidated that HAP1 was downregulated in gastric cancer. What's more, overexpressing HAP1 inhibited cell proliferation, cell migration and invasion, and triggered apoptosis during glucose deprivation. More importantly, the antitumor properties and mechanisms of HAP1 have been elucidated further in gastric cancer.
Taken together, the available evidence implies that HAP1 may serve as a potential tumor suppressor, making it a significant target in preventing and treating gastric cancer. This research provides a theoretical basis for the early diagnosis, clinical targeted therapy, and prognosis evaluation of gastric cancer.
胃癌是一种异质性癌症,其病因复杂。迫切需要探索新的诊断和治疗靶点。亨廷顿蛋白相关蛋白1(HAP1)与亨廷顿舞蹈病(HD)直接相关。然而,亨廷顿舞蹈病患者的癌症发病率较低。因此,我们致力于研究HAP1与胃癌发生发展之间的相关性。
采用免疫组织化学染色、蛋白质免疫印迹分析和逆转录定量聚合酶链反应(RT-qPCR)来探究HAP1在胃癌中的定位和表达。为研究HAP1的生物学意义,我们通过慢病毒感染在MKN28和AGS细胞系中过表达HAP1。为探究HAP1在细胞增殖中的作用,进行了细胞计数实验、5-乙炔基-2'-脱氧尿苷(EdU)掺入实验和集落形成实验。我们进行了伤口愈合实验和Transwell实验来研究细胞迁移和侵袭。为进一步研究HAP1在葡萄糖剥夺期间是否能调节胃癌细胞死亡,进行了膜联蛋白V-异硫氰酸荧光素/碘化丙啶(Annexin V-FITC/PI)染色。在我们的研究中,我们阐明了HAP1在胃癌中表达下调。此外,过表达HAP1可抑制细胞增殖、细胞迁移和侵袭,并在葡萄糖剥夺期间引发细胞凋亡。更重要的是,HAP1在胃癌中的抗肿瘤特性和机制得到了进一步阐明。
综上所述,现有证据表明HAP1可能作为一种潜在的肿瘤抑制因子,使其成为预防和治疗胃癌的重要靶点。本研究为胃癌的早期诊断、临床靶向治疗及预后评估提供了理论依据。