| Autor: |
Kequan Xu, Peng Xia, Xiangdong Gongye, Xiao Zhang, Shuxian Ma, Zhang Chen, Hao Zhang, Jie Liu, Yingyi Liu, Yonghua Guo, Ye Yao, Meng Gao, Yiran Chen, Zhonglin Zhang, Yufeng Yuan |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Molecular Metabolism, Vol 63, Iss , Pp 101540- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2212-8778 |
| DOI: |
10.1016/j.molmet.2022.101540 |
| Popis: |
Objective: Emerging studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in hepatocellular carcinoma (HCC). A rapidly increasing number of studies have shown that metabolic changes including lipid metabolic reprogramming play a significant role in the progression of HCC. But it remains to be elucidated how lncRNAs affect tumor cell metabolism. Methods: Through analysis and screening of The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset, we found a novel lncRNA RP11-386G11.10 was overexpressed, related to prognosis, conserved and non-protein-coding in HCC and related to poor prognosis. Then, CCK-8, colony formation, Transwell invasion, wound healing assays were performed and nude mouse subcutaneous tumour formation and lung metastasis models were established to explore the effect of RP11-386G11.10 on HCC tumour growth and metastasis. Chromatography-mass spectrometry (GC-MS) and Nile red staining detected the effect of RP11-386G11.10 on lipid metabolism in HCC. Mechanistically, we clarified the RP11-386G11.10/miR-345-3p/HNRNPU signalling pathway through dual luciferase reporter, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays and identified ZBTB7A as a transcription factor of RP11-386G11.10. Results: RP11-386G11.10 was overexpressed in HCC and positively correlated with tumour size, TNM stage, and poor prognosis in HCC patients. RP11-386G11.10 promoted the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, RP11-386G11.10 acted as a competing endogenous RNA (ceRNA) for miR-345-3p to regulate the expression of HNRNPU and its downstream lipogenic enzymes, leading to lipid accumulation in HCC cells and promoting their growth and metastasis. In addition, we identified ZBTB7A as a transcription factor of RP11-386G11.10. Moreover, HNRNPU promoted the expression of ZBTB7A in HCC cells, thereby increasing the transcriptional activity of RP11-386G11.10, and forming a positive feedback loop, ultimately leading continuous lipid accumulation, growth and metastasis in HCC cells. Conclusions: Our results indicated that the lncRNA RP11-386G11.10 was a novel oncogenic lncRNA that was strongly correlated with the poor prognosis of HCC. The ZBTB7A-RP11-386G11.10-HNRNPU positive feedback loop promoted the progression of HCC by regulating lipid anabolism. RP11-386G11.10 may become a new diagnostic and prognostic biomarker and therapy target for HCC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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