炎症性肠病患者发生的肠癌分为两种类型：散发型和炎症相关型。目前炎症相关结直肠癌的分子机制研究较少。我们前期发现肠上皮Satb2特异敲除小鼠自发出现肠炎；进行化学诱导后，Satb2缺失小鼠发生的肠炎更严重、肠癌更具侵袭性。由于Satb2缺失小鼠的腹泻症状明显，我们通过16S-rRNA测序发现Satb2缺失和肠道菌群失调有关。此外，SATB2缺失会造成氯离子交换体SLC26A3显著下降。SLC26A3是肠腔氯离子吸收的关键基因，它下降后造成肠腔环境的变化可能是菌群失调的潜在原因。基于此，我们提出SATB2可能通过调控SLC26A3而改变肠腔环境，进而影响肠道菌群，从而在炎症相关结直肠癌中发挥作用。本研究拟应用动物模型、细胞模型及临床标本等明确SATB2及其调控的SLC26A3信号在炎症相关结直肠癌发生中的作用，并探讨肠道菌群在其中的调控机制，最终为炎症相关结直肠癌的治疗和预防提供理论依据。

Colorectal cancer in patients with inflammatory bowel disease may develop two types of colorectal cancer (CRC): sporadic and colitis-associated colorectal cancer (CAC). At present, there are few studies on the molecular mechanism of CAC. Previously, we found that mice with intestinal epithelium-specific knockout of Satb2 spontaneously developed enteritis. After chemical induction, Satb2-deficient mice developed more severe colitis, and more aggressive bowel cancer. Due to the marked symptom of diarrhea in Satb2-deficient mice, and according to 16S-rRNA sequencing we found that Satb2 depletion was associated with intestinal flora imbalance. In addition, the loss of SATB2 caused a significant decrease in the chloride ion exchanger SLC26A3, which is a key gene for chloride ion absorption in colon. Its down-regulation may disrupt the luminal environment and may then cause dysbacteriosis. Accordingly, we propose that SATB2 may play a role in the carcinogenesis of CAC through regulating SLC26A3, thereby changing the luminal environment as well as the intestinal flora. We will further adopt the animal models, cell models and clinical specimens to clarify the role of SATB2 and its regulated SLC26A3 signaling in the carcinogenesis of CAC, and to explore the underlying mechanism through the regulation of intestinal flora. Our study may eventually provide a theoretical basis for the treatment and prevention of CAC.