Journal
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
Volume 40, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13046-021-01836-7
Keywords
Colorectal cancer; Hypoxia; LATS2; Hippo signaling pathway; tRNA half
Categories
Funding
- National Natural Science Foundation of China [81772506, 81972203]
Ask authors/readers for more resources
The study uncovered a specific 5'tiRNA-His-GTG-engaged pathway in CRC progression and provided clues for designing a novel therapeutic target in CRC.
Background 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. Methods 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 (HIF1 alpha) 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. Results 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 HIF1 alpha/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. Conclusions 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available