miR-145在黄斑蓝子鱼HUFA合成调控中的作用及机制研究

弄清鱼类高不饱和脂肪酸(HUFA)合成调控机制有助于解决海水鱼配合饲料对鱼油依赖性过强的问题。近年来本课题组在研究黄斑蓝子鱼HUFA合成代谢调控中，首次报道miR-17通过靶向作用∆4fad基因、miR-33通过与转录因子SREBP共表达参与HUFA的合成调控。最近，我们发现转录因子HNF4α基因的3’非编码区存在miR-145的结合位点，且实验证明它们之间存在互作关系。而前期我们已证实HNF4α参与HUFA的合成调控，这提示miR-145可能以不同于miR-17/33的作用方式调控HUFA的合成。本项目拟对miR-145参与HUFA合成调控的作用机制进行深入研究，包括miR-145靶向作用HNF4α参与HUFA合成代谢的功能确认，miR-145对HNF4α下游基因的调控作用及调控网络分析等。研究成果可为全面揭示鱼类HUFA合成调控机制提供新资料，为研发提高鱼体HUFA合成能力提供新思路。

To clarify the regulatory mechanism of highly unsaturated fatty acids (HUFA) biosynthesis in fish may be helpful to resolve the problem that the formula feed for marine fish is overwhelmingly dependent on fish oil. In recent years, we have been engaged on the research of the metabolism of HUFA biosynthesis in Siganus canaliculatus, and firstly reported that miR-17 was involved in the regulation of HUFA biosynthesis via targeting a fatty acyl desaturase (delta-4 fad), while miR-33 was via cooperating with the transcription factor SREBP in Siganus canaliculatus. Recently, we have found that there was a binding site of miR-145 in the 3’-untranslated region (3’UTR) of HNF4α. And it was demonstrated that an interaction really existed between the 3’UTR of HNF4α and miR-145. We previously demonstrated that HNF4α was a transcription factor that plays an important role in the regulation of HUFA biosynthesis in Siganus canaliculatus. This suggested that the regulation pathway of miR-145 on the HUFA biosynthesis might be different from miR-17 and miR-33. Therefore, we aim to investigate the effects of miR-145 on the HUFA biosynthesis via targeting HNF4α gene as well as its downstream gene expression network. Our study may illuminate the regulatory mechanism of miR-145 on HUFA biosynthesis in Siganus canaliculatus. The results will be helpful to clarify the regulatory mechanism of HUFA biosynthesis in fish and provide new ideas to develop the techniques for fish to increase the capability to produce much more HUFA.