消痰通腑方调控lncRNA-ncRuPAR介导PAR-1/STAT3通路干预结直肠癌发生的作用机制

The pathogenesis of colorectal cancer (CRC) is very complexed, with previous studies suggesting STAT3 signaling plays an important role but with unclear mechanism. We previously revealed that protease-activated receptor-1 (PAR-1) was one of the activators of STAT3 signaling pathway. PAR-1 was a gene target of long-chain non-coding RNA-ncRuPAR, playing an important role in the development of colorectal cancer. Evidence demonstrates Xiaotong Tongfu Decoction upregulates ncRuPAR expression level, inhibits PAR-1 and STAT3 expression levels, resulting in lowered CRC development. We hypothesize that Xiaotan Tongfu Decoction interferes with Colorectal Cancer via ncRuPAR Targeting PAR-1 / STAT3 Pathway.We propose to use ncRuPAR lentivital vector and CRC orthotopic mouse model to investigate the action mechanism of ncRuPAR/PAR-1/STAT3 axis in CRC initiation, and to explore how it is affected by Xiaotan Tongfu Decoction. Our results will help reveal mechanism of CRC initiation and how it is impacted by traditional Chinese medicine.

结直肠癌的发病机制复杂，研究发现STAT3通路在结直肠癌发生中起重要作用，成为肿瘤重要的治疗靶点，但STAT3通路的调控机制尚不清楚，为临床防治带来难题。前期研究发现细胞膜上蛋白酶激活受体PAR-1与STAT3通路激活呈正相关，而PAR-1是长链非编码RNA-ncRuPAR的靶基因，在结直肠癌的发生中起重要作用。消痰通腑方能够抑制AOM/DSS模型小鼠结直肠癌发生，上调ncRuPAR表达，抑制PAR-1和STAT3的表达。因此我们提出假说：消痰通腑方通过ncRuPAR靶向PAR-1/STAT3通路干预结直肠癌发生。本研究通过ncRuPAR差异表达稳定株和小鼠结直肠癌模型，探索ncRuPAR通过PAR-1调控STAT3通路抑制结直肠癌发生的机制，探讨消痰通腑方对ncRuPAR/PAR-1/STAT3的调节作用。这对于揭示结直肠癌发生的机制和阐述中药防治结直肠癌的作用机理具有重要科学意义。

结直肠癌的发病机制复杂，研究发现STAT3通路在结直肠癌发生中起重要作用，成为肿瘤重要的治疗靶点，本研究通过研究发现细胞膜上蛋白酶激活受体PAR-1与STAT3通路激活呈正相关，而PAR-1是长链非编码RNA-ncRuPAR的靶基因，在结直肠癌的发生中起重要作用。本研究通过ncRuPAR差异表达稳定株和小鼠结直肠癌模型，探索ncRuPAR通过PAR-1调控STAT3通路抑制结直肠癌发生的机制，并通过体内体外实验均证实了消痰通腑方对ncRuPAR/PAR-1/STAT3的调节作用，从而验证了“消痰通腑方通过ncRuPAR靶向PAR-1/STAT3通路干预结直肠癌发生”的研究假说。本研究对于揭示结直肠癌发生的机制和阐述中药防治结直肠癌的作用机理具有重要科学意义。

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