A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA
Abstract Background Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. Me...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-06-01
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| Series: | Cellular & Molecular Biology Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11658-023-00463-8 |
| _version_ | 1797789661093953536 |
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| author | Rui Zhao Zhenming Yang Bo Zhao Wenjing Li Yaohui Liu Xiaoxue Chen Jing Cao Jiarui Zhang Yan Guo Licheng Xu Jinpeng Wang Yanan Sun Ming Liu Linli Tian |
| author_facet | Rui Zhao Zhenming Yang Bo Zhao Wenjing Li Yaohui Liu Xiaoxue Chen Jing Cao Jiarui Zhang Yan Guo Licheng Xu Jinpeng Wang Yanan Sun Ming Liu Linli Tian |
| author_sort | Rui Zhao |
| collection | DOAJ |
| description | Abstract Background Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. Methods We elucidated the expression profiles of tsRNAs in four paired LSCC and non-neoplastic tissues by sequencing and verified the sequencing data by quantitative real-time PCR (qRT–PCR) of 60 paired samples. The tyrosine-tRNA derivative tRFTyr was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRFTyr in tumorigenesis of LSCC. Mechanistic experiments including RNA pull-down, parallel reaction monitoring (PRM) and RNA immunoprecipitation (RIP) were employed to uncover the regulatory mechanism of tRFTyr in LSCC. Results tRFTyr was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRFTyr significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRFTyr could enhance the phosphorylated level of lactate dehydrogenase A (LDHA) by interacting with it. The activity of LDHA was also activated, which induced lactate accumulation in LSCC cells. Conclusions Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRFTyr in LSCC. tRFTyr could promote lactate accumulation and tumour progression in LSCC by binding to LDHA. These findings may aid in the development of new diagnostic biomarkers and provide new insights into therapeutic strategies for LSCC. |
| first_indexed | 2024-03-13T01:53:50Z |
| format | Article |
| id | doaj.art-c8b3f2b0cad64189bbf18e10b8793285 |
| institution | Directory Open Access Journal |
| issn | 1689-1392 |
| language | English |
| last_indexed | 2024-03-13T01:53:50Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj.art-c8b3f2b0cad64189bbf18e10b87932852023-07-02T11:20:51ZengBMCCellular & Molecular Biology Letters1689-13922023-06-0128111810.1186/s11658-023-00463-8A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHARui Zhao0Zhenming Yang1Bo Zhao2Wenjing Li3Yaohui Liu4Xiaoxue Chen5Jing Cao6Jiarui Zhang7Yan Guo8Licheng Xu9Jinpeng Wang10Yanan Sun11Ming Liu12Linli Tian13Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversitySchool of Forestry, Northeast Forestry UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical UniversityAbstract Background Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. Methods We elucidated the expression profiles of tsRNAs in four paired LSCC and non-neoplastic tissues by sequencing and verified the sequencing data by quantitative real-time PCR (qRT–PCR) of 60 paired samples. The tyrosine-tRNA derivative tRFTyr was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRFTyr in tumorigenesis of LSCC. Mechanistic experiments including RNA pull-down, parallel reaction monitoring (PRM) and RNA immunoprecipitation (RIP) were employed to uncover the regulatory mechanism of tRFTyr in LSCC. Results tRFTyr was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRFTyr significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRFTyr could enhance the phosphorylated level of lactate dehydrogenase A (LDHA) by interacting with it. The activity of LDHA was also activated, which induced lactate accumulation in LSCC cells. Conclusions Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRFTyr in LSCC. tRFTyr could promote lactate accumulation and tumour progression in LSCC by binding to LDHA. These findings may aid in the development of new diagnostic biomarkers and provide new insights into therapeutic strategies for LSCC.https://doi.org/10.1186/s11658-023-00463-8tsRNAstRFTyrLDHALactateLSCC |
| spellingShingle | Rui Zhao Zhenming Yang Bo Zhao Wenjing Li Yaohui Liu Xiaoxue Chen Jing Cao Jiarui Zhang Yan Guo Licheng Xu Jinpeng Wang Yanan Sun Ming Liu Linli Tian A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA Cellular & Molecular Biology Letters tsRNAs tRFTyr LDHA Lactate LSCC |
| title | A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA |
| title_full | A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA |
| title_fullStr | A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA |
| title_full_unstemmed | A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA |
| title_short | A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA |
| title_sort | novel tyrosine trna derived fragment trftyr induces oncogenesis and lactate accumulation in lscc by interacting with ldha |
| topic | tsRNAs tRFTyr LDHA Lactate LSCC |
| url | https://doi.org/10.1186/s11658-023-00463-8 |
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