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Title:
tRF3008A suppresses the progression and metastasis of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner | Journal of Experimental & Clinical Cancer Research
Description:
Background tRNA-derived fragments (tRFs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of tRFs to colorectal cancer (CRC) remain largely unknown. Methods tRF3008A (a tRFRNA derived from tRNAVal) was identified by RNA sequencing and validated by quantitative reverse transcription PCR. The role of tRF3008A in CRC progression was assessed both in vitro and in vivo, and its downstream target genes were identified and validated in CRC cells. RNA pull-down with mass spectrometry and AGO-RIP were used to confirm the interaction of tRF3008A and AGO proteins. The clinical implications of tRF3008A were assessed in CRC tissues and blood samples. Results The expression of tRF3008A was reduced in colorectal cancer, and its reduction was significantly correlated with advanced and metastatic disease in CRC. Patients with low tRF3008A expression showed significantly shorter DFS, and multivariate analysis identified tRF3008A as an independent prognostic biomarker in CRC. Functionally, tRF3008A inhibits the proliferation and migration of CRC in vivo and in vitro by repressing endogenous FOXK1, a positive regulator of the Wnt/β-catenin pathway. Mechanistically, tRF3008A binds to AGO proteins as a guide to destabilize oncogenic FOXK1 transcript. Conclusions tRF3008A suppresses the metastasis and progression of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner.
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Keywords {🔍}
trfa, cells, cancer, expression, trfs, crc, fig, article, foxk, colorectal, cell, google, scholar, ago, performed, hct, analysis, cas, rna, tissues, trf, mimetic, control, proteins, group, tumor, levels, human, clinical, rnas, protein, wnt, progression, genes, patients, potential, fragments, signaling, data, showed, growth, small, transfected, expressed, trnaderived, pathway, trna, correlation, test, samples,
Topics {✒️}
wnt/β-catenin signaling pathway wnt/β-catenin signaling molecules ice-cold phosphate-buffered saline wnt/β-catenin pathway trf-mediated post-transcriptional silencing rna-binding protein-rna complexes germline-specific piwi clade characterized trna-derived fragments trna-derived rna fragments trna-derived small rna trna-derived small rnas lc-ms/ms analysis obtain complete profile endogenous smrna-mediated tgs differential trf profiles clinical stages i-iii rna-binding protein complexes enter rna-binding complexes employing small-rna sequencing human colon cancer wh dna-binding domain trf3008a-lna-transfected ht29 cells trna-derived fragments potential tumor-suppressive modulators quantitative rt-pcr analysis article download pdf trf-specific divergent primers trf–argonaute protein interaction inhibit protein translation anti–pan-ago antibody human colorectal cancer tumor-suppressive trfs impair mrna target-predicting algorithms trna derived tirna colon cancer cells trf3008a-mediated tumor suppression post-transcriptional silencing dual-luciferase vector colorectal cancer diagnoses wnt pathway inhibitor trf3008a-high ht29 cells nat rev genet shan zeng wnt inhibitor treatment dual-luciferase assays human transfer rna privacy choices/manage cookies trf3008a-low hct116 cells colorectal cancer progression luciferase reporter activity
Questions {❓}
- Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
- Why should cancer biologists care about tRNAs?
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headline:tRF3008A suppresses the progression and metastasis of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner
description:tRNA-derived fragments (tRFs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of tRFs to colorectal cancer (CRC) remain largely unknown. tRF3008A (a tRFRNA derived from tRNAVal) was identified by RNA sequencing and validated by quantitative reverse transcription PCR. The role of tRF3008A in CRC progression was assessed both in vitro and in vivo, and its downstream target genes were identified and validated in CRC cells. RNA pull-down with mass spectrometry and AGO-RIP were used to confirm the interaction of tRF3008A and AGO proteins. The clinical implications of tRF3008A were assessed in CRC tissues and blood samples. The expression of tRF3008A was reduced in colorectal cancer, and its reduction was significantly correlated with advanced and metastatic disease in CRC. Patients with low tRF3008A expression showed significantly shorter DFS, and multivariate analysis identified tRF3008A as an independent prognostic biomarker in CRC. Functionally, tRF3008A inhibits the proliferation and migration of CRC in vivo and in vitro by repressing endogenous FOXK1, a positive regulator of the Wnt/β-catenin pathway. Mechanistically, tRF3008A binds to AGO proteins as a guide to destabilize oncogenic FOXK1 transcript. tRF3008A suppresses the metastasis and progression of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner.
datePublished:2022-01-22T00:00:00Z
dateModified:2022-01-22T00:00:00Z
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tRNA-derived fragments (tRFs)
tRF3008A
FOXK1
AGO
Colorectal cancer
Cancer Research
Immunology
Apoptosis
Oncology
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headline:tRF3008A suppresses the progression and metastasis of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner
description:tRNA-derived fragments (tRFs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of tRFs to colorectal cancer (CRC) remain largely unknown. tRF3008A (a tRFRNA derived from tRNAVal) was identified by RNA sequencing and validated by quantitative reverse transcription PCR. The role of tRF3008A in CRC progression was assessed both in vitro and in vivo, and its downstream target genes were identified and validated in CRC cells. RNA pull-down with mass spectrometry and AGO-RIP were used to confirm the interaction of tRF3008A and AGO proteins. The clinical implications of tRF3008A were assessed in CRC tissues and blood samples. The expression of tRF3008A was reduced in colorectal cancer, and its reduction was significantly correlated with advanced and metastatic disease in CRC. Patients with low tRF3008A expression showed significantly shorter DFS, and multivariate analysis identified tRF3008A as an independent prognostic biomarker in CRC. Functionally, tRF3008A inhibits the proliferation and migration of CRC in vivo and in vitro by repressing endogenous FOXK1, a positive regulator of the Wnt/β-catenin pathway. Mechanistically, tRF3008A binds to AGO proteins as a guide to destabilize oncogenic FOXK1 transcript. tRF3008A suppresses the metastasis and progression of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner.
datePublished:2022-01-22T00:00:00Z
dateModified:2022-01-22T00:00:00Z
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tRNA-derived fragments (tRFs)
tRF3008A
FOXK1
AGO
Colorectal cancer
Cancer Research
Immunology
Apoptosis
Oncology
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address:
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name:Xiangya Hospital, Central South University
address:
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address:
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address:
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name:Xiangya Hospital, Central South University
address:
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address:
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address:
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address:
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address:
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address:
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email:[email protected]
PostalAddress:
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
name:Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
name:Department of Life Science, McMaster University, Hamilton, Canada
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA
name:Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
name:Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
name:Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
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