Kong Qingli, Zhang Zhisheng, Liang Zhipeng
Department of Hepatobiliary Gastrointestinal Surgery, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin City, People's Republic of China.
Anim Cells Syst (Seoul). 2020 Sep 10;24(5):267-274. doi: 10.1080/19768354.2020.1816579.
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 3'-UTR of , 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.
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治疗中具有重要作用。最近发现miR-637对胃癌具有抑制作用，本研究旨在探讨miR-637是否能通过内质网应激调节细胞凋亡。结果显示，衣霉素（TM）诱导胃癌细胞（AGS）中miR-637表达下调，细胞凋亡和内质网应激增加。miR-637过表达促进了TM诱导的细胞凋亡以及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可与 的3'-UTR结合，并负向调节CALR的表达。在AGS细胞中共转染miR-637和CALR表明，CALR过表达可逆转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表达参与内质网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。
