BACKGROUND Long noncoding RNAs (lncRNAs) are emerging as critical regulatory elements and play fundamental roles in the biology of various cancers. However, we are still lack of knowledge about their expression patterns and functions in human colorectal cancer (CRC). METHODS Differentially expressed lncRNAs in CRC were identified by bioinformatics screen and the level of MIR22HG in CRC and control tissues were determined by qRT-PCR. Cell viability and migration capacities were examined by MTT and transwell assay. Mouse model was used to examine the function and rational immunotherapy of MIR22HG in vivo. RESULTS We systematically investigated the expression pattern of lncRNAs and revealed MIR22HG acts as a tumor suppressor in CRC. The expression of MIR22HG was significantly decreased in CRC, which was mainly driven by copy number deletion. Reduced expression of MIR22HG was significantly associated with poor overall survival. Silencing of MIR22HG promoted cell survival, proliferation and tumor metastasis in vitro and in vivo. Mechanistically, MIR22HG exerts its tumor suppressive activity by competitively interacting with SMAD2 and modulating the activity of TGFβ pathway. Decreased MIR22HG promoted the epithelial-mesenchymal transition in CRC. Importantly, we found that MIR22HG expression is significantly correlated with CD8A and overexpression of MIR22HG triggers T cell infiltration, enhancing the clinical benefits of immunotherapy. CONCLUSION MIR22HG acts as a tumor suppressor in CRC. Our data provide mechanistic insights into the regulation of MIR22HG in TGFβ pathway and facilitates immunotherapy in cancer.

中文翻译：

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MIR22HG 通过 TGFβ/SMAD 信号传导充当肿瘤抑制因子，并促进结直肠癌的免疫治疗。

背景长非编码RNA（lncRNA）正在成为关键的调控元件，并在各种癌症的生物学中发挥着基础作用。然而，我们仍然缺乏关于它们在人类结直肠癌（CRC）中的表达模式和功能的了解。方法通过生物信息学筛选鉴定CRC中差异表达的lncRNA，并通过qRT-PCR测定CRC和对照组织中MIR22HG的水平。通过MTT和transwell实验检查细胞活力和迁移能力。利用小鼠模型检验MIR22HG的体内功能和合理的免疫治疗。结果我们系统地研究了 lncRNA 的表达模式，并揭示了 MIR22HG 在 CRC 中充当肿瘤抑制因子。MIR22HG 的表达在 CRC 中显着降低，这主要是由拷贝数缺失驱动的。MIR22HG 表达减少与总体生存率较差显着相关。MIR22HG 沉默可促进体外和体内细胞存活、增殖和肿瘤转移。从机制上讲，MIR22HG 通过与 SMAD2 竞争性相互作用并调节 TGFβ 通路的活性来发挥其肿瘤抑制活性。MIR22HG 的减少促进了 CRC 的上皮间质转化。重要的是，我们发现 MIR22HG 表达与 CD8A 显着相关，并且 MIR22HG 过度表达触发 T 细胞浸润，增强免疫治疗的临床益处。结论 MIR22HG 在 CRC 中充当肿瘤抑制因子。我们的数据为 TGFβ 通路中 MIR22HG 的调节提供了机制见解，并促进癌症的免疫治疗。