IGSF10通过Spi-B和circ-0001821/miR-346/CD74双通路抑制NSCLC转移的机制研究

转移是NSCLC患者死亡的最主要原因。我们通过大样本组学数据筛选出与NSCLC患者预后密切相关的指标IGSF10。前期基础证实，IGSF10通过调控Integrin-β1表达，抑制NSCLC细胞的转移能力。但具体机制尚未明确。前期结果显示：IGSF10通过结合Spi-B减少其入核，在转录水平抑制Integrin-β1表达；IGSF10下调的circ-0001821作为ceRNA，与miR-346竞争性结合，解除对CD74的抑制，促进Integrin-β1表达及活化。因此本研究旨在证实：IGSF10通过Spi-B和circ-0001821-miR-346-CD74双途径，在转录及转录后水平共同调控Integrin-β1表达，抑制NSCLC转移。本研究结果将阐明IGSF10通过调控Integrin-β1表达抑制肺癌转移的机制，为探讨以IGSF10为靶点的肺癌抗转移治疗提供重要科学依据。

Metastasis is the leading cause of death in NSCLC patients. We screened out IGSF10 related to the prognosis of NSCLC patients, through large sample omics data. We have confirmed that IGSF10 inhibits the metastasis ability of lung cancer cells by regulating Integrin-β1 expression. However, the specific mechanism is not clear. The previous results showed that: IGSF10 reduces its nucleus entry by binding Spi-B, inhibits the expression of Integrin-β1 at the transcriptional level. Circ-0001821, which is down-regulated by IGSF10, is used as ceRNA to play the competitive binding effect on miR-346, release the inhibition of CD74, promote the expression and activation of Integrin-β1. This study aims to confirm that IGSF10, through the Spi-B and circ-0001821-miR-346-CD74 dual pathways, together regulates the expression of Integrin-β1 at the transcriptional and post-transcriptional levels and inhibits NSCLC metastasis. The results of this study will clarify the mechanism by which IGSF10 inhibits lung cancer metastasis by regulating the expression of Integrin-β1. It provides an important scientific basis for exploring the anti-metastatic treatment of lung cancer with IGSF10 as the target.