ABSTRACT Gastric cancer is a leading cause of cancer death worldwide. Endoplasmic reticulum (ER) stress-induced apoptosis has been confirmed to be important in the treatment of gastric cancer. MiR-637 has recently been found to exert inhibitory effects on gastric cancer, and this study aimed to investigate whether miR-637 could regulate apoptosis through ER stress. The results showed that tunicamycin (TM) induced downregulation of miR-637 in gastric cancer cells (AGS) and increase of apoptosis and ER stress. Overexpression of miR-637 promoted TM-induced apoptosis and expression of ER stress associated proteins (GRP78 and CHOP), but inhibited expression of Calreticulin. MiR-637 could bind with the 3ʹ-UTR of CALR, and negatively regulated the expression of CALR. The co-transfection of miR-637 and CALR in AGS cells show that, CALR overexpression could reverse the pro-apoptosis effects of miR-637 in TM-treated cells. In conclusion, the present study suggests that miR-637 participates in ER stress-induced apoptosis in gastric cancer cells by suppressing CALR expression. miR-637 or CALR may be a future potential target for gastric cancer treatment.

中文翻译：

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上调miR-637通过抑制钙网蛋白加重内质网应激诱导的胃癌细胞凋亡

摘要 胃癌是全球癌症死亡的主要原因。内质网（ER）应激诱导的细胞凋亡已被证实在胃癌的治疗中很重要。最近发现 MiR-637 对胃癌有抑制作用，本研究旨在探讨 miR-637 是否可以通过 ER 应激调节细胞凋亡。结果表明，衣霉素（TM）诱导胃癌细胞（AGS）中miR-637的下调以及细胞凋亡和ER应激的增加。miR-637 的过表达促进了 TM 诱导的细胞凋亡和内质网应激相关蛋白（GRP78 和 CHOP）的表达，但抑制了钙网蛋白的表达。MiR-637可以与CALR的3ʹ-UTR结合，负向调控CALR的表达。miR-637 和 CALR 在 AGS 细胞中的共转染表明，CALR 过表达可以逆转 miR-637 在 TM 处理细胞中的促凋亡作用。总之，本研究表明miR-637通过抑制CALR表达参与ER应激诱导的胃癌细胞凋亡。miR-637 或 CALR 可能是未来胃癌治疗的潜在靶点。