Department of General Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of Gastrointestinal Surgery, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
RNA Biol. 2022;19(1):548-559. doi: 10.1080/15476286.2021.1992995. Epub 2021 Dec 31.
Recent research unveiled that LINC00857 plays a regulatory role in multiple human cancers, such as lung adenocarcinoma and gastric cancer. Nevertheless, the function of LINC00857 in pancreatic adenocarcinoma (PAAD) remains unclear. This study concentrates on LINC00857 to discuss the relevant molecular mechanism of this gene in PAAD. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot were implemented for measuring the expressions of RNAs and proteins. Wound healing and Transwell assays were used to assess cell migration and invasion, and fluorescent in situ hybridization (FISH) to locate LINC00857 in PAAD cells. Additionally, mechanism assays were conducted to validate the interaction between genes. Results indicated that LINC00857 was upregulated in PAAD cells and the knockdown of LINC00857 impeded PAAD cell migration, invasion and epithelial-mesenchymal transition (EMT). Further, it was found that LNC00857 regulates CLDN12 expression by targeting miR-150-5p. Moreover, LINC00857 was confirmed to recruit serine/arginine-rich splicing factor 1 (SRSF1) to promote the alternative splicing (AS) targeting CLDN12, affecting the phenotypes of PAAD cells. In addition, the transcription factor ZNF460 was proven to positively regulate LINC00857 expression. To sum up, LINC00857 regulated by ZNF460 upregulates CLDN12 expression by sponging miR-150-5p and recruiting SRSF1 to facilitate the progression of PAAD cells.[Figure: see text].
最近的研究表明，LINC00857 在多种人类癌症中发挥着调控作用，如肺腺癌和胃癌。然而，LINC00857 在胰腺导管腺癌（PAAD）中的作用尚不清楚。本研究集中于 LINC00857，探讨该基因在 PAAD 中的相关分子机制。采用定量逆转录聚合酶链反应（RT-qPCR）和 Western blot 检测 RNA 和蛋白质的表达。采用划痕愈合和 Transwell 实验评估细胞迁移和侵袭，荧光原位杂交（FISH）定位 PAAD 细胞中的 LINC00857。此外，还进行了机制实验验证基因之间的相互作用。结果表明，LINC00857 在 PAAD 细胞中上调，敲低 LINC00857 抑制 PAAD 细胞迁移、侵袭和上皮-间充质转化（EMT）。进一步研究发现，LINC00857 通过靶向 miR-150-5p 调控 CLDN12 的表达。此外，LINC00857 被证实招募丝氨酸/精氨酸丰富剪接因子 1（SRSF1）促进靶向 CLDN12 的选择性剪接（AS），影响 PAAD 细胞的表型。此外，转录因子 ZNF460 被证明可正向调控 LINC00857 的表达。综上所述，LINC00857 受 ZNF460 调控，通过海绵吸附 miR-150-5p 和招募 SRSF1 来上调 CLDN12 的表达，促进 PAAD 细胞的进展。[图：见正文]
