Figure 1 Interleukin-34 (IL-34) is an important target gene for miR-28-5p. The experiment used the viral vector provided by Shanghai Jikai Company. Figure 2. Bidirectional regulatory network of miR-28-5p and tumor-associated macrophages (TAM). About the author: Dr. Zhou Shaolai, a resident of the Department of Hepatic Oncology Surgery, Zhongshan Hospital, Fudan University, is mainly engaged in the mechanism of hepatocarcinoma microenvironment regulation of tumor invasion and metastasis. In the past five years, the first author published 10 SCI articles in Gastroenterology and Hepatology. With a cumulative impact factor of 79.8, he cited more than 200 times. At present, as the project leader, he will preside over one project of the National Natural Science Foundation of China and the Shanghai Yangfan Plan. Original text from: Jikai Gene WeChat public number Long press and pay attention Automatic Cable Reel,Automatic Water Hose Reel,Industrial Water Hose Reel,Automatic Garden Hose Reel NINGBO QIKAI ENVIRONMENTAL TECHNOLOGY CO.,LTD , https://www.water-hose-reel.com
miR-28-5p-IL-34-macrophage feedback loop regulates liver cancer metastasis
Professor Zhou Wei reveals a new mechanism of liver cancer metastasis
Prof. Zhou Wei, research team of the Institute of Liver Cancer, Fudan University (Affiliated Zhongshan Hospital) officially published the article "Hepatology" ( hepatology ) in May 2016 "miR-28-5p-IL-34-Macrophage Feedback Loop Modulates Hepatocellular Carcinoma Metastasis" (IF=11.19) . Metastasis is one of the most significant biological features of malignant tumors and the leading cause of death in cancer patients. Tumor invasion and metastasis is a series of complex sequential sequential processes between tumor cells, hosts and tumor microenvironments. A microRNA (miRNA), which usually contains a 22-base short-chain non-coding RNA, functions as an "oncogene" or a "tumor suppressor gene" by regulating the expression of a functional gene at a post-transcriptional level. Professor Zhou Wei's research team conducted a series of complete and meticulous research processes to screen key miRNAs involved in liver cancer metastasis and conduct a series of studies on its functions. First, the researchers screened human hepatocarcinoma cells with different metastatic potentials for RNA-seq screening, and found that the key miRNA of liver cancer metastasis: miR-28-5p was abnormally expressed and negatively correlated with cell line metastatic potential; miR-28 was also found. -5p only has the effect of promoting liver cancer metastasis in the body. Further, TargetScan bioinformatics prediction combined with cytokine/chemokine PCR chip was used to screen and verify that the important target gene miR-28-5p is interleukin-34 (IL-34) (see Figure 1). Previous studies have shown that IL-34 binds to the colony-stimulating factor receptor CSFIR expressed on the surface of monocytes and stimulates macrophage activation. This study found that IL-34 activates FAK and ERK1/2 signaling pathways in vitro and promotes macrophage proliferation and chemotaxis. In animal experiments, upregulation of IL-34 in hepatoma cells promotes tumor cell growth and lung metastasis, increasing intratumoral macrophage infiltration. It is worth noting that the researchers found that the macrophage secreting cytokine TGF-β1 forms a feedback loop involved in the regulation of IL-34 by miR-28-5p (see Figure 2). Finally, immunohistochemical analysis of liver cancer samples showed that miR-28-5p was significantly negatively correlated with IL-34 expression in tumor tissues, and was significantly associated with macrophage infiltration, short overall survival, and recurrence of tumor patients. Multivariate analysis showed that miR-28-5p low expression/IL-34 overexpression or simultaneous presence with intratumoral macrophages was an independent prognostic indicator of overall survival and cancer recurrence (see Figure 2). The results of this study creatively mapped the two-way regulatory network of microRNAs and tumor-associated macrophages (TAMs) in liver cancer cells, revealing new mechanisms and potential molecular targets for liver cancer metastasis regulation.