HNRNPA1P10通过Sp1/vasohibin-1磷酸化途径调控结直肠癌远处转移的作用机制研究

Distant metastasis is one of the most important factors affecting the prognosis of colorectal cancer and the molecular mechanism is still unclear. Our preliminary data showed that HNRNPA1P10 regulated the transcription of vasohibin-1 gene through phosphorylation of its transcription factor Sp1, playing an important role in distant metastasis of colorectal cancer. The phosphorylation of Sp1 might serve as the crucial step and the underlying mechanism remains unknown. In this study, the mechanism of HNRNPA1P10 regulating phosphorylation of Sp1 as “scaffold” and “molecular decoy” will be investigated; carcinoma oncogenesis model will be used to verify the mechanism of HNRNPA1P10 regulating the metastasis of colorectal cancer through the phosphorylation pathway of Sp1/vasohibin-1; the expression of HNRNPA1P10, Sp1 and vasohibin-1 in colorectal cancer tissues and metastatic tissues as well as the relationship between their expression and clinical pathological parameters will be analyzed. Our study will clarify the mechanism of HNRNPA1P10 regulating distant metastasis of colorectal cancer through the phosphorylation pathway of Sp1/vasohibin-1, which might contribute a new target to the treatment of distant metastasis from colorectal cancer.

远处转移是导致结直肠癌预后差的重要因素，其分子机制尚未完全明确。我们前期通过长链非编码RNA（lncRNA）芯片、生物信息学、功能学实验等筛选出结直肠癌远处转移相关的关键lncRNA：HNRNPA1P10，可能通过调节转录因子Sp1的蛋白磷酸化水平，调控靶基因vasohibin-1的转录而发挥作用，具体机制未见报道。本课题拟在体外实验中探索HNRNPA1P10通过“脚手架”和“分子诱饵”作用调控Sp1磷酸化及其转录功能的机制；在裸鼠体内验证HNRNPA1P10通过Sp1/vasohibin-1磷酸化途径调控结直肠癌转移的作用；在结直肠癌组织中分析HNRNPA1P10、Sp1、vasohibin-1等的表达水平及其与结直肠癌转移的关系。旨在阐明HNRNPA1P10通过Sp1/vasohibin-1磷酸化途径调节结直肠癌远处转移的作用机制，为结直肠癌远处转移治疗提供新靶点。

远处转移是导致结直肠癌预后差的重要因素，其分子机制尚未完全明确。我们前期通过长链非编码RNA（lncRNA）芯片、生物信息学、功能学实验等筛选出结直肠癌远处转移相关lncRNA：HNRNPA1P10，可能通过调节转录因子Sp1的蛋白磷酸化水平，调控靶基因vasohibin-1的转录而发挥作用，具体机制未见报道。本课题在体外实验中探索HNRNPA1P10通过“脚手架”和“分子诱饵”作用调控Sp1磷酸化及其转录功能的机制；在裸鼠体内验证HNRNPA1P10通过Sp1/vasohibin-1磷酸化途径调控结直肠癌转移的作用；在结直肠癌组织中分析HNRNPA1P10、vasohibin-1等的表达及其与肿瘤转移的关系。本课题初步阐明HNRNPA1P10通过Sp1磷酸化途径调节结直肠癌远处转移的作用机制，为结直肠癌远处转移提供新的潜在治疗靶点。