MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish.
MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish.
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microRNA-21通过斑马鱼PI 3 K/AKT、STAT 3和PDCD 4/TNF-α信号通路在结肠炎相关癌和结直肠癌中发挥多种肿瘤代谢作用
DOI：
10.3390/cancers13215565
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发表时间：
2021-11-06
期刊：
影响因子：
5.2
通讯作者：
Her GM
中科院分区：
文献类型：
--
作者：
Lai CY;Yeh KY;Liu BF;Chang TM;Chang CH;Liao YF;Liu YW;Her GM
PI3K/AKT、STAT3和PDCD4/TNF-α信号网络由microRNA (miR)-21调控，对炎症调节、肿瘤抑制调节和致癌激活至关重要。我们开发了一种斑马鱼模型（ImiR-21），可诱导miR-21过表达，特别是在肠道中。miR-21过表达导致炎症性肠病引起的结直肠癌（CRC）的发展。此外，在该模型中，结直肠癌的生理、代谢和组织学方面与肠道致癌物偶氮氧甲烷或葡聚糖硫酸钠诱导的结肠炎相关癌（CAC）相似。因此，miR-21对CRC/CAC的发病机制至关重要，可以作为治疗CRC/CAC的新的治疗靶点。结直肠癌（CRC）是全球癌症相关死亡的主要原因。炎症性肠病（IBD）患者发展为结直肠癌的风险很高。炎症细胞因子受复杂的基因网络和调控rna，尤其是microrna的调控。MicroRNA-21 （miR-21）是炎症反应和癌症发展中最常上调的microrna之一。miR-21已成为多种疾病的遗传和药理调控靶点。然而，肠道炎症和肿瘤发生之间的关系在很大程度上是未知的。因此，在本研究中，我们建立了一个斑马鱼模型（ImiR-21），在肠道中诱导miR-21过表达。结果表明，miR-21可通过PI3K/AKT、PDCD4/TNF-α和IL-6/STAT3信号网络在ImiR-21中诱导结直肠癌或结肠炎相关癌（CAC）。miR-21激活PI3K/AKT和NF-κB信号通路，导致初始炎症；此后，miR-21和TNF-α抑制PDCD4及其抑瘤活性。最终，活跃的STAT3刺激了强烈的炎症反应，激活了肿瘤细胞的侵袭/转移过程。因此，我们的研究结果表明，miR-21通过PI3K/AKT、STAT3和PDCD4/TNF-α信号网络对CRC/CAC的发展至关重要。
The PI3K/AKT, STAT3, and PDCD4/TNF-α signaling networks, regulated by the microRNA (miR)-21, are critical for inflammatory regulation, tumor suppressor modulation, and oncogenic activation. We developed a zebrafish model (ImiR-21) with an inducible overexpression of miR-21, specifically in the intestine. The miR-21 overexpression resulted in the development of colorectal cancer (CRC) due to inflammatory bowel disease. Furthermore, the physiological, metabolic, and histological aspects of CRC were similar to those of colitis-associated cancer (CAC) induced by the intestinal carcinogens azoxymethane or dextran sodium sulfate in this model. Thus, miR-21 is critical to the pathogenesis of CRC/CAC and could serve as a novel therapeutic target to treat CRC/CAC. Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Patients with inflammatory bowel disease (IBD) have a high risk of developing CRC. Inflammatory cytokines are regulated by complex gene networks and regulatory RNAs, especially microRNAs. MicroRNA-21 (miR-21) is amongst the most frequently upregulated microRNAs in inflammatory responses and cancer development. miR-21 has become a target for genetic and pharmacological regulation in various diseases. However, the association between inflammation and tumorigenesis in the gut is largely unknown. Hence, in this study, we generated a zebrafish model (ImiR-21) with inducible overexpression of miR-21 in the intestine. The results demonstrate that miR-21 can induce CRC or colitis-associated cancer (CAC) in ImiR-21 through the PI3K/AKT, PDCD4/TNF-α, and IL-6/STAT3 signaling network. miR-21 activated the PI3K/AKT and NF-κB signaling pathways, leading to initial inflammation; thereafter, miR-21 and TNF-α repressed PDCD4 and its tumor suppression activity. Eventually, active STAT3 stimulated a strong inflammatory response and activated the invasion/metastasis process of tumor cells. Hence, our findings indicate that miR-21 is critical for the development of CRC/CAC via the PI3K/AKT, STAT3, and PDCD4/TNF-α signaling networks.
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影响因子：
8
作者：
Kaler, P.;Augenlicht, L.;Klampfer, L.
通讯作者：
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影响因子：
7.3
作者：
Jacouton E;Chain F;Sokol H;Langella P;Bermúdez-Humarán LG
通讯作者：
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影响因子：
4.4
作者：
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Hirano T
影响因子：
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作者：
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炎症和大肠癌：结肠炎相关的肿瘤。
影响因子：
9
作者：
Grivennikov, Sergei I.
通讯作者：
Grivennikov, Sergei I.