Wu Hui, Li Anshu, Zheng Qichang, Gu Jingyang, Zhou Wei
Research Center, Shanghai Healink Medical Information Consulting Co., LTD, Shanghai, 201102, China.
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer Cell Int. 2023 Jul 4;23(1):130. doi: 10.1186/s12935-023-02979-7.
The 5 year survival rate after diagnosis of pancreatic cancer (PANC) is less than 5%, and it is one of the malignant tumors with the worst prognosis. Identification of novel oncogenes involved in the occurrence of pancreatic cancer is of great significance to improve the overall survival of PANC patients. Our previous study found that miR-532 is a key factor in PANC occurrence and development, and this study further explored its mechanism. We found that the expression of lncRNA LZTS1-AS1 was elevated in PANC tumor tissues and cells, and correlated with poor prognosis. In vitro experiments confirmed that LZTS1-AS1 could promote proliferation, oncogenicity, migration, and invasion of PANC cells, and inhibit apoptosis and autophagy. However, miR-532 had the completely opposite effect, and inhibition of miR-532 counteracted the effect of LZTS1-AS1 on PANC cells. Dual luciferase gene reporter assay and RNA immunoprecipitation assay confirmed the targeting relationship between LZTS1-AS1 and miR-532, and their expression levels were negatively correlated in PANC tissues. Overexpression of TWIST1 could counteract the effect of miR-532 in PANC cells, and the expression levels of both were negatively changed in PANC tissues and cells. Our results suggest that lncRNA LZTS1-AS1 acts as an oncogene to promote the metastasis of PANC and inhibit autophagy, and its mechanism may be to regulate TWIST1 through sponge miR-532. This study provides novel biomarkers and therapeutic targets for PANC.
胰腺癌（PANC）诊断后的5年生存率低于5%，是预后最差的恶性肿瘤之一。鉴定参与胰腺癌发生的新致癌基因对提高PANC患者的总生存率具有重要意义。我们之前的研究发现miR-532是PANC发生发展的关键因素，本研究进一步探讨其机制。我们发现lncRNA LZTS1-AS1在PANC肿瘤组织和细胞中的表达升高，且与预后不良相关。体外实验证实，LZTS1-AS1可促进PANC细胞的增殖、致癌性、迁移和侵袭，并抑制凋亡和自噬。然而，miR-532具有完全相反的作用，抑制miR-532可抵消LZTS1-AS1对PANC细胞的作用。双荧光素酶基因报告基因检测和RNA免疫沉淀检测证实了LZTS1-AS1与miR-532之间的靶向关系，且它们在PANC组织中的表达水平呈负相关。TWIST1的过表达可抵消miR-532在PANC细胞中的作用，且二者在PANC组织和细胞中的表达水平均呈负向变化。我们的结果表明，lncRNA LZTS1-AS1作为一种致癌基因促进PANC的转移并抑制自噬，其机制可能是通过海绵状miR-532调节TWIST1。本研究为PANC提供了新的生物标志物和治疗靶点。
