Sun Changpeng, Guan Hongjun, Li Jinjin, Gu Yinfeng
Department of Cardiothoracic Surgery, Jianhu Clinical Medical College of Yangzhou University, No. 666, Nanhuan Road, Jinhu Town, Jianhu, Yancheng City, Jiangsu Province, 224700, PR China.
Department of Cardiothoracic Surgery, Jianhu Clinical Medical College of Yangzhou University, Yancheng City, Jiangsu Province, 224700, PR China.
Open Med (Wars). 2023 Feb 16;18(1):20230641. doi: 10.1515/med-2023-0641. eCollection 2023.
Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancers, which are the main killer of cancer-related death worldwide. Circular RNA (circRNA) has been found to modulate NSCLC development. However, the role of circ_0000376 in NSCLC development has been underreported. The present work showed that circ_0000376 and 3-phos-phoinositide-dependent protein kinase-1 (PDPK1) expression were dramatically increased, but miR-545-3p was decreased in NSCLC tissues and cells. circ_0000376 expression was closely associated with lymph node metastasis, tumor-node-metastasis stage, and tumor size of NSCLC patients. circ_0000376 knockdown repressed NSCLC cell proliferation, migration, invasion, and glutaminolysis but induced cell apoptosis. Additionally, miR-545-3p bound to circ_0000376, and circ_0000376 regulated cell phenotypes by associating with miR-545-3p. MiR-545-3p also participated in NSCLC cell proliferation, migration, invasion, apoptosis, and glutaminolysis by targeting PDPK1. Further, circ_0000376 absence repressed tumor formation . Collectively, circ_0000376 regulated NSCLC cell tumor properties by the miR-545-3p/PDPK1 axis, suggesting that circ_0000376 could be employed as a therapeutic target for NSCLC.
非小细胞肺癌（NSCLC）占肺癌总数的80%，是全球癌症相关死亡的主要杀手。环状RNA（circRNA）已被发现可调节NSCLC的发展。然而，circ_0000376在NSCLC发展中的作用报道较少。目前的研究表明，circ_0000376和3-磷酸肌醇依赖性蛋白激酶-1（PDPK1）在NSCLC组织和细胞中的表达显著增加，但miR-545-3p表达降低。circ_0000376的表达与NSCLC患者的淋巴结转移、肿瘤-淋巴结-转移分期和肿瘤大小密切相关。敲低circ_0000376可抑制NSCLC细胞的增殖、迁移、侵袭和谷氨酰胺分解，但诱导细胞凋亡。此外，miR-545-3p与circ_0000376结合，circ_0000376通过与miR-545-3p结合来调节细胞表型。miR-545-3p还通过靶向PDPK1参与NSCLC细胞的增殖、迁移、侵袭、凋亡和谷氨酰胺分解。此外，circ_0000376缺失可抑制肿瘤形成。总之，circ_0000376通过miR-545-3p/PDPK1轴调节NSCLC细胞的肿瘤特性，提示circ_0000376可作为NSCLC的治疗靶点。
