MicroRNA-196a-5p/IκBα/NFKB轴在结直肠癌肝转移射频消融术后非消融区肿瘤进展中的作用及机制研究

RFA accelerates tumor progression in the colon cancer liver metastasis of postoperative ablation area, seriously restricts the clinical application of RFA. A recent study found that miR-196a has high expression in colon cancer patients serum, tissue and cell, but also can promote the proliferation,invasion and metastasis of tumor cell, and inhibit tumor cell apoptosis and enhance tumor drug resistance. Previous studies found that miR-196a expressed higher of intrahepatic the ablation area after RFA than normal tumor tissue, miR-196a can regulate EMT of the colon cancer cells through NFKB, and miR-196a-5p has a targeted relationship with IkBα. All applicants put forward that RFA promotes miR-196a high expression in the ablation area colon cancer liver metastases cells, miR-196a regulates NFKB to induce EMT to promote tumor progression by the target genes IKBα. This project intends to further study the molecular mechanisms of the tumor progression in the colon cancer liver metastasis of postoperative ablation area through animal and cell experiment. Research results will help to reveal the core factor of the tumor progression in the colon cancer liver metastasis of postoperative ablation area and provide new ideas for targeted therapy, it has important significance to improve the prognosis and survival rate of the colorectal cancer liver metastasis after RFA.

射频消融（RFA）加速结肠癌肝转移术后非消融区肿瘤进展，严重制约了RFA的临床应用。近期研究发现miR-196a在结肠癌患者血清、组织及细胞中均呈高表达，而且能够促进肿瘤细胞增殖、侵袭及转移，抑制肿瘤细胞凋亡并增强肿瘤耐药性。前期研究发现，RFA术后肝内非消融区肿瘤组织比正常瘤组织miR-196a表达升高，miR-196a 能通过NFKB通路调控结肠癌细胞上皮间质转化（EMT），且miR-196a-5p与IkBα存在靶向关系。综上申请人提出：RFA促进非消融区结肠癌肝转移细胞miR-196a高表达，并通过靶基因IKBα调控NFKB信号通路诱导EMT促进肿瘤进展。本项目拟通过动物及细胞实验深入研究RFA对结直肠癌肝转移术后非消融区肿瘤进展的分子机制。研究成果将有助于揭示结直肠癌肝转移RFA后非消融区肿瘤进展的核心因子，为靶向治疗提供新思路，对提高结直肠癌肝转移RFA预后和生存率具有重要意义。

射频消融（RFA）加速结肠癌肝转移术后非消融区肿瘤进展，严重制约了RFA的临床应用。近期研究发现miR-196a在结肠癌患者血清、组织及细胞中均呈高表达，而且能够促进肿瘤细胞增殖、侵袭及转移，抑制肿瘤细胞凋亡并增强肿瘤耐药性。前期研究发现，RFA术后肝内非消融区肿瘤组织比正常瘤组织miR-196a表达升高，miR-196a 能通过NFKB通路调控结肠癌细胞上皮间质转化（EMT），且miR-196a-5p与IkBα存在靶向关系。进一步验证RFA促进非消融区结肠癌肝转移细胞miR-196a高表达，并通过靶基因IKBα调控NFKB信号通路诱导EMT促进肿瘤进展。本项目通过动物及细胞实验深入研究RFA对结直肠癌肝转移术后非消融区肿瘤进展的分子机制。研究成果将有助于揭示结直肠癌肝转移RFA后非消融区肿瘤进展的核心因子，为靶向治疗提供新思路，对提高结直肠癌肝转移RFA预后和生存率具有重要意义