LncRNA MIF-AS1通过与CTCF和HDAC2相互作用抑制IQGAP2转录调节结直肠癌细胞的增殖凋亡

长链非编码RNA(LncRNA)分子与结直肠癌(CRC)发生发展关系密切。预实验用抗肿瘤药物CUDC-101处理细胞后测序得到差异表达的LncRNA MIF-AS1和IQGAP2基因。MIF-AS1表达下调，在CRC中充当致癌基因的作用。用RNA-pulldown联合质谱技术鉴定与MIF-AS1结合的蛋白发现：MIF-AS1与转录因子CTCF及HDAC2存在互作；ChIP实验提示CTCF对IQGAP2启动子区存在转录调控作用；MIF-AS1招募HDAC2、CTCF形成转录复合物抑制IQGAP2表达。据此我们猜测：CUDC-101通过抑制转录复合物CTCF/MIF-AS1/HDAC2活性，提高IQGAP2表达，抑制结直肠癌细胞增殖和转移，促进凋亡。本项目将通过体内外实验，深入探讨MIF-AS1在CRC细胞增殖与凋亡中的作用机制，为肿瘤精准诊疗提供新靶标。

Long non-coding RNA (LncRNA) molecules are closely related to the occurrence and development of colorectal cancer (CRC). In the preliminary experiments, CRC cells were treated with the anti-tumor drug CUDC-101 and the differentially expressed LncRNA MIF-AS1 and IQGAP2 genes were obtained through RNA-seq. MIF-AS1 is down-regulated and acts as an oncogene in CRC. We conducted RNA-pulldown combined with mass spectrometry to identify proteins that cooperate with MIF-AS1. It was found that MIF-AS1 interacts with the transcription factor CTCF and HDAC2. ChIP experiments indicated that CTCF transcriptionally regulated the promoter region of IQGAP2. Moreover, MIF-AS1 can recruit HDAC2 and CTCF to form a transcription complex, which reduces IQGAP2 expression. Based on this, we make a hypothesis: CUDC-101 inhibits the formation of the transcription complex CTCF/MIF-AS1/HDAC2, increases the expression of IQGAP2, inhibits the proliferation and metastasis, promotes apoptosis of colorectal cancer cells. This project will thoroughly explore the mechanism of MIF-AS1 in the proliferation and apoptosis of CRC through in vivo and in vitro experiments. Thus, provide a new target for precise diagnosis and treatment of colorectal cancer.