NLRX1调控的线粒体自噬在胰腺癌发生发展中的作用及机制研究

Pancreatic cancer is known as the "king of cancer", the five-year survival rate is less than 8%, and there is no effective targeted drug for the treatment of pancreatic cancer. Finding important signaling molecules involved in the occurrence and development of pancreatic cancer will provide new drug targets for the clinical treatment of pancreatic cancer. Mitophagy is an important way for cells to resist external stress. However, the function of mitophagy in the occurrence and development of pancreatic cancer is still unclear. Our previous study found that NLRX1, a member of innate immune family receptor, is a new type of mitophagy receptor, and NLRX1 is highly expressed in pancreatic cancer cell lines. The reactive oxygen species (ROS) content of pancreatic cancer cells with NLRX1 knockdown is increased and the growth rate is significantly slowed down. However, NLRX1 knockdown did not affect the growth of normal cells. We speculate that NLRX1 may be involved in the occurrence and development of pancreatic cancer by mediating mitophagy. Next, we will further clarify the expression and regulation mechanism of NLRX1 in pancreatic cancer, confirm that NLRX1 regulates mitophagy in pancreatic cancer and promotes the occurrence and development of pancreatic cancer by inhibiting the production of ROS. This study will provide potential molecular targets and theoretical basis for the diagnosis and treatment of pancreatic cancer.

胰腺癌被称为“癌中之王”，五年生存率不足8%，现今临床上并无有效的治疗胰腺癌的靶向药物。寻找参与胰腺癌发生发展的重要信号分子将为胰腺癌的临床治疗提供新的药物靶点。线粒体自噬是细胞抵抗外界应激的重要途径，其在胰腺癌发生发展中的机制仍不清楚。我们前期研究发现先天免疫家族受体成员NLRX1是一个新型线粒体自噬受体，并且NLRX1在胰腺癌细胞株中高表达，NLRX1敲低的胰腺癌细胞活性氧含量升高，同时生长速度明显减慢，然而NLRX1并不影响正常细胞的生长。我们推测NLRX1可能通过介导线粒体自噬促进胰腺癌的发生发展过程。接下来我们将进一步明确NLRX1在胰腺癌发展过程中的表达调控机制，证实NLRX1调控胰腺癌线粒体自噬过程并通过抑制活性氧产生促进胰腺癌的发生发展。此研究将为胰腺癌的诊疗提供潜在的分子靶点和理论依据。

胰腺癌被称为“癌中之王”，其特点是发现晚，进展快，治疗难，其五年生存率不足8%。由于胰腺癌对于常规的肿瘤疗法，如放疗和化疗不敏感，并且现在临床上无对应的靶向药物，因此在其他类型的肿瘤纷纷被攻克的今天，胰腺癌的临床治疗仍是肿瘤研究领域的重点和难点，因此研究和发现胰腺癌早期筛查靶点，以及介导胰腺癌发生发展的重要信号通路和相关分子至关重要。线粒体自噬是生物体对于线粒体质量控制的重要步骤，也是细胞应对外界应激，如低氧和营养物质缺乏等环境进化出的细胞自我保护机制。我们的研究首次发现，NLRX1介导的线粒体自噬促进胰腺癌的发生发展。首先，NLRX1特异性的在胰腺癌中高表达；其次，NLRX1通过介导线粒体自噬，进而影响细胞内活性氧的产生，从而促进了胰腺癌的发生；最后，通过抑制线粒体自噬可以抑制胰腺癌类器官的生长。本研究为胰腺癌的防治提供了新的分子靶点和理论依据。