lncRNAFGD5-AS1/IGF2BP2通过m6A识别途径介导FGD5mRNA稳定性促进胰腺癌侵袭转移的机制研究

反义长链非编码RNA（lncRNA）与其正义链mRNA的相互调控在肿瘤的恶性进展中发挥关键作用，然而其调控机制不明确。研究发现lncRNA可通过RNA的N6-甲基腺嘌呤(m6A)修饰调控RNA的转录与翻译促进胰腺癌的侵袭转移。申请人前期发现：①FGD5-AS1在胰腺癌中高表达，与胰腺癌的远处转移及预后密切相关。②FGD5-AS1促进FGD5的表达和RNA稳定性。③FGD5-AS1可与IGF2BP2相互作用介导FGD5m6A位点的识别。④FGD5可能是Rho信号通路的激活蛋白。因此，申请人提出科学假设：FGD5-AS1与IGF2BP2通过m6A识别作用促进FGD5的mRNA稳定性及表达上调，进而激活Rho信号通路增强胰腺癌侵袭转移能力。本项目将以FGD5-AS1为研究对象，深入阐述m6A在FGD5mRNA稳定性上调及胰腺癌侵袭转移中的调控机制，为临床治疗提供可能的靶点。

The mutual regulation of antisense long-chain noncoding RNA (lncRNA) and its sense-strand mRNA plays a key role in the malignant progression of tumors, but its regulatory mechanism is not clear. Studies have found that lncRNA can regulate the transcription and translation of RNA through the modification of RNA N6-methyladenine (m6A) to promote pancreatic cancer metastasis. The applicant previously found : ① FGD5-AS1 is highly expressed in pancreatic cancer, which is closely related to the distant metastasis and prognosis of pancreatic cancer. ② FGD5-AS1 promotes FGD5 expression and RNA stability. ③ FGD5-AS1 can interact with IGF2BP2 to mediate the recognition of FGD5 m6A site. ④FGD5 may be an activator protein of Rho signaling pathway. Therefore, the applicant proposed a scientific hypothesis: FGD5-AS1 and IGF2BP2 promote the mRNA stability and expression of FGD5 through m6A recognition, and then activate the Rho signaling pathway to enhance the invasion and metastasis ability of pancreatic cancer. This project will take FGD5-AS1 as the research object, in-depth elaborate the regulatory mechanism of m6A in the upregulation of FGD5 mRNA stability and pancreatic cancer invasion and metastasis, then provide a possible target for clinical treatment.