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         headline:A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2
         description:Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear. Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5’tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5’tiRNA-His-GTG. The regulation of 5’tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments. Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5’tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5’tiRNA-His-GTG in CRC and found that targeting 5’tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5’tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5’tiRNA-His-GTG, which renders 5’tiRNA-His-GTG to “turn off” hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes. In summary, the findings revealed a specific 5’tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.
         datePublished:2021-02-15T00:00:00Z
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            Hypoxia
            LATS2
            Hippo signaling pathway
            tRNA half
            Cancer Research
            Immunology
            Apoptosis
            Oncology
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                        name:Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, Shanghai, China
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      headline:A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2
      description:Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear. Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5’tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5’tiRNA-His-GTG. The regulation of 5’tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments. Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5’tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5’tiRNA-His-GTG in CRC and found that targeting 5’tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5’tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5’tiRNA-His-GTG, which renders 5’tiRNA-His-GTG to “turn off” hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes. In summary, the findings revealed a specific 5’tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.
      datePublished:2021-02-15T00:00:00Z
      dateModified:2021-02-15T00:00:00Z
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      sameAs:https://doi.org/10.1186/s13046-021-01836-7
      keywords:
         Colorectal cancer
         Hypoxia
         LATS2
         Hippo signaling pathway
         tRNA half
         Cancer Research
         Immunology
         Apoptosis
         Oncology
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