A p53/lnc‐Ip53 Negative Feedback Loop Regulates Tumor Growth and Chemoresistance
| العنوان: | A p53/lnc‐Ip53 Negative Feedback Loop Regulates Tumor Growth and Chemoresistance |
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| المؤلفون: | Shi-Mei Zhuang, Li-Zhen Zhang, Yu-Wei Luo, Yunfei Yuan, Jine Yang, Feng-Ting Liu |
| المصدر: | Advanced Science, Vol 7, Iss 21, Pp n/a-n/a (2020) Advanced Science |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | p53, General Chemical Engineering, General Physics and Astronomy, Medicine (miscellaneous), 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), Downregulation and upregulation, In vivo, Gene silencing, General Materials Science, lcsh:Science, acetylation, Full Paper, Cell growth, Chemistry, Binding protein, General Engineering, Full Papers, 021001 nanoscience & nanotechnology, Non-coding RNA, HDAC1, 0104 chemical sciences, tumor growth, Acetylation, non‐coding RNA, Cancer research, lcsh:Q, 0210 nano-technology, lnc‐Ip53 |
| الوصف: | Acetylation is a critical mechanism to modulate tumor‐suppressive activity of p53, but the causative roles of long non‐coding RNAs (lncRNAs) in p53 acetylation and their biological significance remain unexplored. Here, lncRNA LOC100294145 is discovered to be transactivated by p53 and is thus designated as lnc‐Ip53 for lncRNA induced by p53. Furthermore, lnc‐Ip53 impedes p53 acetylation by interacting with histone deacetylase 1 (HDAC1) and E1A binding protein p300 (p300) to prevent HDAC1 degradation and attenuate p300 activity, resulting in abrogation of p53 activity and subsequent cell proliferation and apoptosis resistance. Mouse xenograft models reveal that lnc‐Ip53 promotes tumor growth and chemoresistance in vivo, which is attenuated by an HDAC inhibitor. Silencing lnc‐Ip53 inhibits the growth of xenografts with wild‐type p53, but not those expressing acetylation‐resistant p53. Consistently, lnc‐Ip53 is upregulated in multiple cancer types, including hepatocellular carcinoma (HCC). High levels of lnc‐Ip53 is associated with low levels of acetylated p53 in human HCC and mouse xenografts, and is also correlated with poor survival of HCC patients. These findings identify a novel p53/lnc‐Ip53 negative feedback loop in cells and indicate that abnormal upregulation of lnc‐Ip53 represents an important mechanism to inhibit p53 acetylation/activity and thereby promote tumor growth and chemoresistance, which may be exploited for anticancer therapy. Acetylation is indispensable for activation of tumor suppressor p53. LncRNA lnc‐Ip53 is induced by p53 and in turn represses p53 acetylation by interacting with HDAC1 and p300 to prevent HDAC1 degradation and attenuate p300 activity, which consequently abrogates p53 activity and thus facilitates cell proliferation and apoptosis resistance. Abnormal upregulation of lnc‐Ip53 in tumors promotes tumor growth and confers chemoresistance. |
| اللغة: | English |
| تدمد: | 2198-3844 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::787ffb43861b39dafd4f00ce46e178e1 https://doaj.org/article/2a7d094d8d6341c29dd5fd0330a8345c |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....787ffb43861b39dafd4f00ce46e178e1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21983844 |
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