LncRNA SLC2A1-AS1/miR-30a-5p/SPOCK1轴调控胆囊癌增殖转移的机制研究

胆囊癌恶性程度高，非编码RNA在胆囊癌中发挥重要作用。申请人前期发现miR-30a-5p显著抑制胆囊癌增殖、转移等生物学功能，但具体的分子调控网络机制尚未可知。预实验中我们通过RNAseq分析，结合表达谱芯片及生物信息学分析，筛选出SLC2A1-AS1和SPOCK1。进一步双荧光素酶报告基因实验发现SLC2A1-AS1、SPOCK1均可和miR-30a-5p的3’UTR区域结合，据此我们推测SLC2A1-AS1和SPOCK1可能作为ceRNA参与miR-30a-5p抑制胆囊癌生物学功能的过程。本项目拟通过细胞分子实验和动物实验等体内外方法研究SLC2A1-AS1、SPOCK1与miR-30a-5p的相互作用关系，探讨三者在调控胆囊癌生物学功能中的作用，阐明SLC2A1-AS1/miR-30a-5p/SPOCK1分子调控网络影响胆囊癌发生发展的机制，为胆囊癌的治疗寻找新的分子靶点。

Gallbladder carcinoma (GBC) is a highly malignant disease, and non-coding RNA plays an important role in GBC. We have found that miR-30a-5p significantly inhibits GBC cell proliferation and metastasis, but the molecular mechanism remains to be determined. In previous study, we identified SLC2A1-AS1 and SPOCK1 by RNA sequencing analysis, expression profile and bioinformatics analysis. Dual luciferase assay confirmed that both SLC2A1-AS1 and SPOCK1 target 3’UTR region of miR-30a-5p. We speculate that SLC2A1-AS1 and SPOCK1 may regulate miR-30a-5p-mediated inhibition of GBC biology as ceRNA. On this basis, we intend to further analyze the interaction between SLC2A1-AS1, SPOCK1 and miR-30a-5p by in vitro and in vivo studies such as cellular biology assays and animal experiments, as well as their function in GBC. Besides, we aim to elucidate the mechanism of SLC2A1-AS1/miR-30a-5p/SPOCK1 molecular regulation network in affecting the occurrence and development of GBC, and provide new molecular targets for the treatment of GBC.