LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1
Abstract Purpose Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-022-02817-2 |
| _version_ | 1811179147975720960 |
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| author | Feng-Chih Kuo Yu-Ting Wang Chia-Hsin Liu Yao-Feng Li Chieh-Hua Lu Sheng-Chiang Su Jhih-Syuan Liu Peng-Fei Li Chia-Luen Huang Li-Ju Ho Chien-Ming Lin Chien-Hsing Lee |
| author_facet | Feng-Chih Kuo Yu-Ting Wang Chia-Hsin Liu Yao-Feng Li Chieh-Hua Lu Sheng-Chiang Su Jhih-Syuan Liu Peng-Fei Li Chia-Luen Huang Li-Ju Ho Chien-Ming Lin Chien-Hsing Lee |
| author_sort | Feng-Chih Kuo |
| collection | DOAJ |
| description | Abstract Purpose Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles and downstream regulatory mechanisms in papillary thyroid cancer cells. Methods We applied three thyroid cancer cell lines (MDA-T32, MDA-T41 and K1) to investigate the phenotypic influence after gain or loss of HOTAIR. The Cancer Genome Atlas (TCGA) database were utilised to select candidate genes possibly regulated by HOTAIR with validation in the cellular system and immunohistochemical (IHC) staining of PTC tissues. Results We observed HOTAIR was highly expressed in MDA-T32 cells but presents significantly decreased levels in MDA-T41 and K1 cells. HOTAIR knockdown in MDA-T32 cells significantly suppressed proliferation, colony formation, migration with cell cycle retardation at G1 phase. On the contrary, HOTAIR overexpression in MDA-T41 cells dramatically enhanced proliferation, colony formation, migration with cell cycle driven toward S and G2/M phases. Similar phenotypic effects were also observed as overexpressing HOTAIR in K1 cells. To explore novel HOTAIR downstream mechanisms, we analyzed TCGA transcriptome in PTC tissues and found DLX1 negatively correlated to HOTAIR, and its lower expression associated with reduced progression free survival. We further validated DLX1 gene was epigenetically suppressed by HOTAIR via performing chromatin immunoprecipitation. Moreover, IHC staining shows a significantly stepwise decrease of DLX1 protein from normal thyroid tissues to stage III PTC tissues. Conclusions Our study pointed out that HOTAIR is a key regulator of cellular malignancy and its epigenetic suppression on DLX1 serves as a novel biomarker to evaluate the PTC disease progression. |
| first_indexed | 2024-04-11T06:29:53Z |
| format | Article |
| id | doaj.art-b9459937fde14254a7c07967fef37426 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-11T06:29:53Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-b9459937fde14254a7c07967fef374262022-12-22T04:40:11ZengBMCCancer Cell International1475-28672022-12-0122111310.1186/s12935-022-02817-2LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1Feng-Chih Kuo0Yu-Ting Wang1Chia-Hsin Liu2Yao-Feng Li3Chieh-Hua Lu4Sheng-Chiang Su5Jhih-Syuan Liu6Peng-Fei Li7Chia-Luen Huang8Li-Ju Ho9Chien-Ming Lin10Chien-Hsing Lee11Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDepartment and Graduate Institute of Life Biochemistry, National Defense Medical CenterDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDepartment of Pathology, Tri-Service General Hospital, National Defense Medical CenterDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterDepartment of Pediatrics, Tri-Service General Hospital, National Defense Medical CenterDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterAbstract Purpose Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles and downstream regulatory mechanisms in papillary thyroid cancer cells. Methods We applied three thyroid cancer cell lines (MDA-T32, MDA-T41 and K1) to investigate the phenotypic influence after gain or loss of HOTAIR. The Cancer Genome Atlas (TCGA) database were utilised to select candidate genes possibly regulated by HOTAIR with validation in the cellular system and immunohistochemical (IHC) staining of PTC tissues. Results We observed HOTAIR was highly expressed in MDA-T32 cells but presents significantly decreased levels in MDA-T41 and K1 cells. HOTAIR knockdown in MDA-T32 cells significantly suppressed proliferation, colony formation, migration with cell cycle retardation at G1 phase. On the contrary, HOTAIR overexpression in MDA-T41 cells dramatically enhanced proliferation, colony formation, migration with cell cycle driven toward S and G2/M phases. Similar phenotypic effects were also observed as overexpressing HOTAIR in K1 cells. To explore novel HOTAIR downstream mechanisms, we analyzed TCGA transcriptome in PTC tissues and found DLX1 negatively correlated to HOTAIR, and its lower expression associated with reduced progression free survival. We further validated DLX1 gene was epigenetically suppressed by HOTAIR via performing chromatin immunoprecipitation. Moreover, IHC staining shows a significantly stepwise decrease of DLX1 protein from normal thyroid tissues to stage III PTC tissues. Conclusions Our study pointed out that HOTAIR is a key regulator of cellular malignancy and its epigenetic suppression on DLX1 serves as a novel biomarker to evaluate the PTC disease progression.https://doi.org/10.1186/s12935-022-02817-2lncRNAHOTAIRPapillary thyroid cancerDLX1 |
| spellingShingle | Feng-Chih Kuo Yu-Ting Wang Chia-Hsin Liu Yao-Feng Li Chieh-Hua Lu Sheng-Chiang Su Jhih-Syuan Liu Peng-Fei Li Chia-Luen Huang Li-Ju Ho Chien-Ming Lin Chien-Hsing Lee LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1 Cancer Cell International lncRNA HOTAIR Papillary thyroid cancer DLX1 |
| title | LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1 |
| title_full | LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1 |
| title_fullStr | LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1 |
| title_full_unstemmed | LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1 |
| title_short | LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1 |
| title_sort | lncrna hotair impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing dlx1 |
| topic | lncRNA HOTAIR Papillary thyroid cancer DLX1 |
| url | https://doi.org/10.1186/s12935-022-02817-2 |
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