Xu Jin, Xu Weixue, Yang Xuan, Liu Zhen, Zhao Yiya, Sun Qinyun
Department of General Surgery, Shengjing Hospital of China Medical University, No.36, Sanhao Street, Heping District, Shenyang, 110004, China.
Cancer Cell Int. 2021 Dec 15;21(1):674. doi: 10.1186/s12935-021-02189-z.
Pancreatic cancer (PCa) is a fatal malignancy with poor prognosis, high recurrence and mortality. Substantial reports have suggested long non-coding RNAs (lncRNAs) are implicated in development of numerous malignant tumors, and PCa is included. However, the correlation between novel lncRNA mir-99a-let-7c cluster host gene (MIR99AHG) and PCa remains elusive and needs to be deeply investigated.
In this study, we firstly used RT-qPCR to examine MIR99AHG expression. Functional assays were implemented for determination of the role of MIR99AHG in PCa cells. Mechanism experiments were designed and carried out for exploring the regulatory mechanism involving MIR99AHG.
MIR99AHG was distinctly overexpressed in PCa cell lines. MIR99AHG deficiency abrogated PCa cell proliferation, migration and invasion. Moreover, MIR99AHG up-regulation was induced by transcription factor forkhead box A1 (FOXA1). Furthermore, MIR99AHG modulated notch receptor 2 (NOTCH2) expression and stimulated Notch signaling pathway through sequestering microRNA-3129-5p (miR-3129-5p) and recruiting ELAV like RNA binding protein 1 (ELAVL1).
Altogether, the exploration of FOXA1/MIR99AHG/miR-3129-5p/ELAVL1/NOTCH2 axis in the progression of PCa might provide a meaningful revelation for PCa diagnosis and treatment.
胰腺癌（PCa）是一种预后差、复发率和死亡率高的致命恶性肿瘤。大量报道表明，长链非编码RNA（lncRNAs）与多种恶性肿瘤的发生发展有关，胰腺癌也不例外。然而，新型lncRNA mir-99a-let-7c簇宿主基因（MIR99AHG）与胰腺癌之间的相关性仍不明确，需要深入研究。
在本研究中，我们首先使用RT-qPCR检测MIR99AHG的表达。进行功能试验以确定MIR99AHG在胰腺癌细胞中的作用。设计并开展机制实验以探索涉及MIR99AHG的调控机制。
MIR99AHG在胰腺癌细胞系中明显过表达。MIR99AHG缺失可消除胰腺癌细胞的增殖、迁移和侵袭能力。此外，转录因子叉头框A1（FOXA1）可诱导MIR99AHG上调。此外，MIR99AHG通过螯合微小RNA-3129-5p（miR-3129-5p）并招募ELAV样RNA结合蛋白1（ELAVL1）来调节Notch受体2（NOTCH2）的表达并激活Notch信号通路。
总之，对FOXA1/MIR99AHG/miR-3129-5p/ELAVL1/NOTCH2轴在胰腺癌进展中的探索可能为胰腺癌的诊断和治疗提供有意义的启示。
