Tian Yongjing, Sun Haibin, Bao Yinshengboer, Feng Haiping, Pang Jian, En Riletu, Jiang Hongliang, Wang Tengqi
Department of Gastrointestinal Surgery, Inner Mongolia Bayannur Hospital, Inner Mongolia, 015000, China.
Department of Cancer Center, Inner Mongolia Bayannur Hospital, No. 98, Ulan Buhe Road, Bayan Nur, Inner Mongolia, 015000, China.
Biochem Genet. 2023 Apr;61(2):809-822. doi: 10.1007/s10528-022-10281-w. Epub 2022 Sep 30.
Gastric cancer (GC) is one of the most prevalent malignancies worldwide. Endoplasmic reticulum (ER) stress plays a key role in the progression of GC. Rapid proliferation of tumor cells interferes with ER homeostasis, leading to ER stress and triggering unfolded protein response. Therefore, it is very necessary to investigate abnormally expressed ER resident proteins (ERp) in cancer cells. This study aimed to investigate the possible roles of ERp44. The mRNA and protein expression of genes were detected using qRT-PCR and western blot. Cell apoptosis was calculated using flow cytometry. Cell proliferation was determined using CCK-8 and colony formation assay. Cell migration was detected by wound healing, and cell invasion was measured by transwell assay. We found that ERp44 was obviously decreased in GC tissues. Furthermore, ERp44 overexpression distinctly suppressed the proliferation, migration, and invasion of MGC-803 and KATO III cells. In contrast, apoptosis was promoted by ERp44 overexpression. Furthermore, mechanistic studies revealed that overexpression of ERp44 inhibited malignant biological processes by regulating the eIF-2α/CHOP signaling pathway. Taken together, our data demonstrated that ERp44 regulated the proliferation, migration, invasion, and apoptosis via ERp44/eIF-2α/CHOP axis in GC. Targeting the ERp44and ER stress may be a promising strategy for GC.
胃癌（GC）是全球最常见的恶性肿瘤之一。内质网（ER）应激在GC进展中起关键作用。肿瘤细胞的快速增殖干扰了内质网稳态，导致内质网应激并触发未折叠蛋白反应。因此，研究癌细胞中异常表达的内质网驻留蛋白（ERp）非常必要。本研究旨在探讨ERp44的可能作用。使用qRT-PCR和蛋白质印迹法检测基因的mRNA和蛋白质表达。使用流式细胞术计算细胞凋亡。使用CCK-8和集落形成试验测定细胞增殖。通过伤口愈合检测细胞迁移，通过Transwell试验测量细胞侵袭。我们发现ERp44在GC组织中明显降低。此外，ERp44过表达明显抑制了MGC-803和KATO III细胞的增殖、迁移和侵袭。相反，ERp44过表达促进了细胞凋亡。此外，机制研究表明，ERp44过表达通过调节eIF-2α/CHOP信号通路抑制恶性生物学过程。综上所述，我们的数据表明，ERp44通过GC中的ERp44/eIF-2α/CHOP轴调节增殖、迁移、侵袭和凋亡。靶向ERp44和内质网应激可能是GC的一种有前景的策略。
