中文摘要
侵袭转移是影响大肠癌预后的重要因素,长链非编码RNA-MALAT1在大肠癌侵袭转移中起重要作用,但MALAT1的调控机制尚不清楚。我们前期研究发现,COX-2/PGE2能够上调MALAT1转录表达,磷酸化STAT3;健脾解毒方能够抑制大肠癌转移,下调COX-2和MALAT1表达。因此,我们提出COX-2/PGE2通过MALAT1激活STAT3信号通路促进大肠癌侵袭转移的科学假说。.本研究采用CRISPER/cas9基因编辑等技术,研究COX-2/PGE2通过MALAT1激活STAT3信号通路促进大肠癌侵袭转移的机制,并深入探讨健脾解毒方对COX-2/PGE2--MALAT1--STAT3生物信息传递的调节机制。这对于揭示大肠癌侵袭转移的机制,明确中药防治大肠癌的作用靶点,具有重要的科学意义。
英文摘要
The prognosis of colorectal cancer (CRC) is critically affected by tumor cell invasion and metastasis. Long non-coding RNA-MALAT1 plays a key role in the metastasis of human colorectal cancer, but the underlying regulation mechanism of MALAT1 expression remains elusive. Our preliminary data have shown that COX-2/PGE2 enhanced MALAT1 expression, and increased the phosphorylation levels of STAT3 protein; Jianpi Jiedu Recipe (JPJDR) downregulated COX-2 and MALAT1 expression, consequently inhibited CRC invasion and metastasis. Hence we here propose the COX-2/PGE2 regulates colorectal cancer metastasis via MALAT1 mediated STAT3 signaling pathway.. In this proposed research project, we propose to use the CRISPR/cas9 genomic editing technology, to delineate this aforementioned mechanism that COX-2/PGE2 activates STAT3 signaling pathway via MALAT1, and elucidate how Jianpi Jiedu Recipe affects it. This study of ours will shed light on the mechanisms by which CRC metastasize and identify novel therapeutical targets for TCM.
