Dataset related to article "Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer"

This record contains raw data related to article “Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer"

Background: Sphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap.

Methods: We screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2-/-) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2-/-Lgr5-EGFP- mice.

Results: S1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/minmouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2-/- mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN.

Conclusions: In normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.

本数据集包含与研究论文《揭示鞘氨醇-1-磷酸受体2（sphingosine-1-phosphate receptor 2, S1PR2）作为上皮干细胞增殖制动器及结直肠癌（colorectal cancer, CRC）肿瘤抑制因子的作用》相关的原始数据。

背景：鞘氨醇-1-磷酸受体2（S1PR2）可介导涵盖细胞增殖、存活与迁移的多效性功能，该功能网络在癌症中普遍失调。目前关于S1PR2是否参与结直肠癌发生发展的相关研究信息较为匮乏，本研究旨在填补这一空白。

方法：我们对76例人类结直肠癌及配对正常黏膜标本中的S1PR2表达变化进行了检测。我们分别在野生型（S1PR2+/+）与S1PR2敲除（S1PR2-/-）小鼠中，对比了炎症驱动型和基因工程构建的结直肠癌模型的造模差异。我们在RKO细胞中重新构建S1PR2的稳定表达，并评估其在异种移植瘤中的生长特性。在功能层面，我们通过向S1PR2+/+类器官（organoids）中加入JTE013来模拟正常黏膜中S1PR2的功能缺失，并对分离自S1PR2-/-Lgr5-EGFP-小鼠的肠上皮干细胞进行了系统表征。

结果：本研究中，33%的结直肠癌样本存在S1PR2表达完全缺失；55%的样本中S1PR2表达显著下调，仅12%的样本保留了与正常黏膜相当的S1PR2表达水平。与S1PR2+/+对照组小鼠相比，S1PR2-/-小鼠的结肠炎诱导型及基因工程Apc+/min结直肠癌模型中，癌组织及高级别腺瘤的发生率、体积和数量均显著升高，且小鼠体内肠道上皮细胞增殖水平增强。S1PR2的缺失会损伤黏膜再生功能，最终促进肠干细胞的扩增。而过表达S1PR2则会减弱细胞周期进程，降低AKT的磷酸化水平，并上调PTEN的表达丰度。

结论：在正常结肠隐窝中，S1PR2的表达伴随肠上皮细胞分化而被激活，但在肠干细胞中无表达；其通过促进上皮分化、阻止干细胞扩增并抑制其恶性转化，从而拮抗肠道肿瘤发生。对于表达高水平Lgr5的结直肠癌患者，靶向调控S1PR2可能具有潜在的治疗价值。