A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2
Abstract 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) progressi...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2021-02-01
|
Series: | Journal of Experimental & Clinical Cancer Research |
Subjects: | |
Online Access: | https://doi.org/10.1186/s13046-021-01836-7 |
id |
doaj-42810800150646029bd227a1d8d2bcc4 |
---|---|
record_format |
Article |
spelling |
doaj-42810800150646029bd227a1d8d2bcc42021-02-21T12:05:42ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-02-0140111710.1186/s13046-021-01836-7A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2En-Wei Tao0Hao-Lian Wang1Wing Yin Cheng2Qian-Qian Liu3Ying-Xuan Chen4Qin-Yan Gao5Division 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 HospitalDivision 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 HospitalInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong KongDivision 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 HospitalDivision 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 HospitalDivision 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 HospitalAbstract 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 (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. 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 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. 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.https://doi.org/10.1186/s13046-021-01836-7Colorectal cancerHypoxiaLATS2Hippo signaling pathwaytRNA half |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
En-Wei Tao Hao-Lian Wang Wing Yin Cheng Qian-Qian Liu Ying-Xuan Chen Qin-Yan Gao |
spellingShingle |
En-Wei Tao Hao-Lian Wang Wing Yin Cheng Qian-Qian Liu Ying-Xuan Chen Qin-Yan Gao A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2 Journal of Experimental & Clinical Cancer Research Colorectal cancer Hypoxia LATS2 Hippo signaling pathway tRNA half |
author_facet |
En-Wei Tao Hao-Lian Wang Wing Yin Cheng Qian-Qian Liu Ying-Xuan Chen Qin-Yan Gao |
author_sort |
En-Wei Tao |
title |
A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2 |
title_short |
A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2 |
title_full |
A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2 |
title_fullStr |
A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2 |
title_full_unstemmed |
A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2 |
title_sort |
specific trna half, 5’tirna-his-gtg, responds to hypoxia via the hif1α/ang axis and promotes colorectal cancer progression by regulating lats2 |
publisher |
BMC |
series |
Journal of Experimental & Clinical Cancer Research |
issn |
1756-9966 |
publishDate |
2021-02-01 |
description |
Abstract 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 (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. 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 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. 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. |
topic |
Colorectal cancer Hypoxia LATS2 Hippo signaling pathway tRNA half |
url |
https://doi.org/10.1186/s13046-021-01836-7 |
work_keys_str_mv |
AT enweitao aspecifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT haolianwang aspecifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT wingyincheng aspecifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT qianqianliu aspecifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT yingxuanchen aspecifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT qinyangao aspecifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT enweitao specifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT haolianwang specifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT wingyincheng specifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT qianqianliu specifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT yingxuanchen specifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 AT qinyangao specifictrnahalf5tirnahisgtgrespondstohypoxiaviathehif1aangaxisandpromotescolorectalcancerprogressionbyregulatinglats2 |
_version_ |
1724258483984924672 |