LncRNA SNHG17 interacts with LRPPRC to stabilize c-Myc protein and promote G1/S transition and cell proliferation
| Autor: | Zhan-Li Chen, Jin-Yu Liu, Ya-Jing Chen, Yun-Long Wang, Shi-Mei Zhuang, Huan-Hui Feng, Jine Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Immunology Cell Models Biological Article S Phase Proto-Oncogene Proteins c-myc Mice Cell growth Cellular and Molecular Neuroscience Downregulation and upregulation Ubiquitin Cell Line Tumor medicine Animals Humans Gene silencing Gene Silencing Phosphorylation Small nucleolar RNA Cell Proliferation biology QH573-671 Protein Stability Chemistry G1 Phase G1/S transition Oncogenes Cell Biology Cell cycle Neoplasm Proteins Up-Regulation Cell biology Gene Expression Regulation Neoplastic HEK293 Cells medicine.anatomical_structure Long non-coding RNAs biology.protein RNA Long Noncoding Cytology |
| Zdroj: | Cell Death and Disease, Vol 12, Iss 11, Pp 1-13 (2021) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Oncogenic c-Myc is a master regulator of G1/S transition. Long non-coding RNAs (lncRNAs) emerge as new regulators of various cell activities. Here, we found that lncRNA SnoRNA Host Gene 17 (SNHG17) was elevated at the early G1-phase of cell cycle. Both gain- and loss-of function studies disclosed that SNHG17 increased c-Myc protein level, accelerated G1/S transition and cell proliferation, and consequently promoted tumor cell growth in vitro and in vivo. Mechanistically, the 1-150-nt of SNHG17 physically interacted with the 1035-1369-aa of leucine rich pentatricopeptide repeat containing (LRPPRC) protein, and disrupting this interaction abrogated the promoting role of SNHG17 in c-Myc expression, G1/S transition, and cell proliferation. The effect of SNHG17 in stimulating cell proliferation was attenuated by silencing c-Myc or LRPPRC. Furthermore, silencing SNHG17 or LRPPRC increased the level of ubiquitylated c-Myc and reduced the stability of c-Myc protein. Analysis of human hepatocellular carcinoma (HCC) tissues revealed that SNHG17, LRPPRC, and c-Myc were significantly upregulated in HCC, and they showed a positive correlation with each other. High level of SNHG17 or LRPPRC was associated with worse survival of HCC patients. These data suggest that SNHG17 may inhibit c-Myc ubiquitination and thus enhance c-Myc level and facilitate proliferation by interacting with LRPPRC. Our findings identify a novel SNHG17-LRPPRC-c-Myc regulatory axis and elucidate its roles in G1/S transition and tumor growth, which may provide potential targets for cancer therapy. |
| Databáze: | OpenAIRE |
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