Wang Kaiqiong, Chen Zhiju, Qiao Xin, Zheng Jinfang
Department of Hepatobiliary Surgery, Hainan Provincial People's Hospital, Haikou 570311, Hainan Province, China.
Department of Gastrointestinal Surgery, Hainan Provincial People's Hospital, Haikou 570311, Hainan Province, China.
Toxicol Res (Camb). 2023 Apr 29;12(3):457-467. doi: 10.1093/toxres/tfad032. eCollection 2023 Jun.
Pancreatic ductal adenocarcinoma, one of the deadliest tumors of the digestive tract, is a difficult and invasive malignancy. Current treatment for pancreatic ductal adenocarcinoma mainly depends on surgery combined with radiotherapy and chemotherapy, which, however, often resulting in questionable curative effect. Therefore, new targeted therapies are needed in future treatment. We first interfered with hsa_circ_0084003 expression in pancreatic ductal adenocarcinoma cells, and further studied how hsa_circ_0084003 functioned in regulating pancreatic ductal adenocarcinoma cell aerobic glycolysis and epithelial-mesenchymal transition, and also evaluated the regulatingeffect of hsa_circ_0084003 on hsa-miR-143-3p and its target DNA methyltransferase 3A. Hsa_circ_0084003 knockdown could notably inhibit the aerobic glycolysis and epithelial-mesenchymal transition of pancreatic ductal adenocarcinoma cells. Mechanistically, hsa_circ_0084003 could regulate its downstream target DNA methyltransferase 3A by binding to hsa-miR-143-3p, and overexpression of hsa_circ_0084003 could reverse the anticarcinogenic effect of hsa-miR-143-3p on aerobic glycolysis and epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells. Hsa_circ_0084003, as a carcinogenic circular RNA, regulated its downstream target DNA methyltransferase 3A to promote pancreatic ductal adenocarcinoma cell aerobic glycolysis and epithelial-mesenchymal transition through sponging hsa-miR-143-3p. Therefore, hsa_circ_0084003 could be studied as a possible therapeutic target regarding pancreatic ductal adenocarcinoma.
胰腺导管腺癌是消化道最致命的肿瘤之一，是一种难治性侵袭性恶性肿瘤。目前胰腺导管腺癌的治疗主要依靠手术联合放疗和化疗，然而，其疗效往往不尽人意。因此，未来的治疗需要新的靶向治疗方法。我们首先干扰胰腺导管腺癌细胞中hsa_circ_0084003的表达，并进一步研究hsa_circ_0084003在调节胰腺导管腺癌细胞有氧糖酵解和上皮-间质转化中的作用，同时评估hsa_circ_0084003对hsa-miR-143-3p及其靶标DNA甲基转移酶3A的调控作用。敲低hsa_circ_0084003可显著抑制胰腺导管腺癌细胞的有氧糖酵解和上皮-间质转化。机制上，hsa_circ_0084003可通过与hsa-miR-143-3p结合来调节其下游靶标DNA甲基转移酶3A，过表达hsa_circ_0084003可逆转hsa-miR-143-3p对胰腺导管腺癌细胞有氧糖酵解和上皮-间质转化的抗癌作用。hsa_circ_0084003作为一种致癌性环状RNA，通过吸附hsa-miR-143-3p来调节其下游靶标DNA甲基转移酶3A，从而促进胰腺导管腺癌细胞的有氧糖酵解和上皮-间质转化。因此，hsa_circ_0084003有望作为胰腺导管腺癌的一个潜在治疗靶点进行研究。
