Department of abdominal surgery, Jiangxi Cancer Hospital, Nanchang, China.
Department of General Surgery, Affiliated Hospital of Jiaxing University, Jiaxing, China.
J Cell Mol Med. 2021 Oct;25(20):9826-9836. doi: 10.1111/jcmm.16930. Epub 2021 Sep 19.
Long non-coding RNAs (lncRNAs) biological functions and molecular mechanisms associated with pancreatic cancer (PC) remain to be poorly elucidated. We aimed to clarify the role of lncRNA LINC00261 (LINC00261) in PC and confirm its regulatory mechanisms. Bioinformatics analysis, RNA pull-down and RIP assays were performed to investigate relationship between LINC00261 and forkhead box P3 (FOXP3). Further, dual-luciferase reporter gene and ChIP assays were employed to confirm the relationship among LINC00261, FOXP3 and sterol carrier protein-2 (SCP2). PC cells were introduced with a series of vectors to verify the effects of LINC00261 and SCP2 on the viability, cell cycle progression, migration and angiogenesis of PC cells. Nude mice with the xenograft tumour were used to evaluate the effects LINC00261 on the tumourigenicity. LINC00261 was lowly expressed in PC tissues and cells. SCP2 was inhibited by LINC00261 through FOXP3. Functionally, upregulated LINC00261 or downregulated SCP2 led to reduced cell viability, migration, angiogenesis and tumourigenicity potentials. This study demonstrated the inhibitory role of LINC00261 in the angiogenesis and cell cycle progression of PC cells. It acts through the negative regulation of SCP2 via targeting FOXP3. Findings in this study highlight a potentially biomarker for PC treatment.
长链非编码 RNA（lncRNA）与胰腺癌（PC）相关的生物学功能和分子机制仍未得到充分阐明。我们旨在阐明 lncRNA LINC00261（LINC00261）在 PC 中的作用，并证实其调节机制。通过生物信息学分析、RNA 下拉和 RIP 测定来研究 LINC00261 与叉头框 P3（FOXP3）之间的关系。进一步，通过双荧光素酶报告基因和 ChIP 测定来证实 LINC00261、FOXP3 和甾醇载体蛋白-2（SCP2）之间的关系。将一系列载体引入 PC 细胞，以验证 LINC00261 和 SCP2 对 PC 细胞活力、细胞周期进程、迁移和血管生成的影响。使用带有异种移植肿瘤的裸鼠来评估 LINC00261 对肿瘤发生的影响。LINC00261 在 PC 组织和细胞中低表达。LINC00261 通过 FOXP3 抑制 SCP2。功能上，上调 LINC00261 或下调 SCP2 导致细胞活力、迁移、血管生成和致瘤性潜力降低。这项研究表明 LINC00261 抑制 PC 细胞的血管生成和细胞周期进程。它通过靶向 FOXP3 负调控 SCP2 发挥作用。本研究的结果突出了 LINC00261 作为 PC 治疗潜在生物标志物的作用。
