The long noncoding RNA TINCR promotes self-renewal of human liver cancer stem cells through autophagy activation
Abstract Hepatocellular carcinoma (HCC) is an extraordinarily heterogeneous tumor, which holds high recurrence and metastasis rates. Liver cancer stem cells (LCSCs) have been considered to be important influencing factors of these pathological properties, but the underlying mechanisms are poorly und...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05424-1 |
| _version_ | 1811319267851763712 |
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| author | Jing Shi Cao Guo Yang Li Junli Ma |
| author_facet | Jing Shi Cao Guo Yang Li Junli Ma |
| author_sort | Jing Shi |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) is an extraordinarily heterogeneous tumor, which holds high recurrence and metastasis rates. Liver cancer stem cells (LCSCs) have been considered to be important influencing factors of these pathological properties, but the underlying mechanisms are poorly understood in HCC. Considerable evidences have shown that autophagy has an important role in cancer stemness. However, it is still unknown whether a long noncoding RNA (lncRNA) TINCR is involved in autophagy and self-renewal maintenance of HCC. In this study, TINCR was found to be highly expressed in HCC tissues and LCSCs. In vitro and in vivo assays for the first time showed that TINCR was required for LCSC self-renewal and tumorigenesis. Moreover, gene ontology analysis revealed the involvement of autophagy in the maintenance of TINCR-regulated stemness. Mechanically, TINCR was associated with polypyrimidine tract binding protein 1 (PTBP1) protein, which further promoted the transcription activity of autophagy related gene ATG5. In conclusion, we demonstrated that TINCR regulated LCSC self-renewal by autophagy activation through PTBP1/ATG5 regulatory pathway, offering a potential new target for HCC therapy. |
| first_indexed | 2024-04-13T12:39:50Z |
| format | Article |
| id | doaj.art-28302de9eb8a49239c4480f792c79e3e |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-13T12:39:50Z |
| publishDate | 2022-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-28302de9eb8a49239c4480f792c79e3e2022-12-22T02:46:33ZengNature Publishing GroupCell Death and Disease2041-48892022-11-01131111110.1038/s41419-022-05424-1The long noncoding RNA TINCR promotes self-renewal of human liver cancer stem cells through autophagy activationJing Shi0Cao Guo1Yang Li2Junli Ma3Affiliated Hospital of Qinghai UniversityInstitute of Medical Sciences, Xiangya Hospital, Central South UniversityAffiliated Hospital of Jining Medical UniversityAffiliated Hospital of Jining Medical UniversityAbstract Hepatocellular carcinoma (HCC) is an extraordinarily heterogeneous tumor, which holds high recurrence and metastasis rates. Liver cancer stem cells (LCSCs) have been considered to be important influencing factors of these pathological properties, but the underlying mechanisms are poorly understood in HCC. Considerable evidences have shown that autophagy has an important role in cancer stemness. However, it is still unknown whether a long noncoding RNA (lncRNA) TINCR is involved in autophagy and self-renewal maintenance of HCC. In this study, TINCR was found to be highly expressed in HCC tissues and LCSCs. In vitro and in vivo assays for the first time showed that TINCR was required for LCSC self-renewal and tumorigenesis. Moreover, gene ontology analysis revealed the involvement of autophagy in the maintenance of TINCR-regulated stemness. Mechanically, TINCR was associated with polypyrimidine tract binding protein 1 (PTBP1) protein, which further promoted the transcription activity of autophagy related gene ATG5. In conclusion, we demonstrated that TINCR regulated LCSC self-renewal by autophagy activation through PTBP1/ATG5 regulatory pathway, offering a potential new target for HCC therapy.https://doi.org/10.1038/s41419-022-05424-1 |
| spellingShingle | Jing Shi Cao Guo Yang Li Junli Ma The long noncoding RNA TINCR promotes self-renewal of human liver cancer stem cells through autophagy activation Cell Death and Disease |
| title | The long noncoding RNA TINCR promotes self-renewal of human liver cancer stem cells through autophagy activation |
| title_full | The long noncoding RNA TINCR promotes self-renewal of human liver cancer stem cells through autophagy activation |
| title_fullStr | The long noncoding RNA TINCR promotes self-renewal of human liver cancer stem cells through autophagy activation |
| title_full_unstemmed | The long noncoding RNA TINCR promotes self-renewal of human liver cancer stem cells through autophagy activation |
| title_short | The long noncoding RNA TINCR promotes self-renewal of human liver cancer stem cells through autophagy activation |
| title_sort | long noncoding rna tincr promotes self renewal of human liver cancer stem cells through autophagy activation |
| url | https://doi.org/10.1038/s41419-022-05424-1 |
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