Open AccessInactivation of the tumor suppressor p53 by long noncoding RNA RMRP
Author(s) -
Yajie Chen,
Qian Hao,
Shanshan Wang,
Mingming Cao,
Yun Huang,
Xiaoling Weng,
Jieqiong Wang,
Zhen Zhang,
Xiong He,
Hua Lu,
Xiang Zhou
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2026813118
Subject(s) - transcription (linguistics) , cancer research , carcinogenesis , biology , rna , microbiology and biotechnology , chemistry , cancer , biochemistry , genetics , gene , philosophy , linguistics
Significance The tumor suppressor p53 prevents tumorigenesis, while inactivation of p53 promotes cancer development and drug resistance. Here, we identify that a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), promotes growth and proliferation of colorectal cancer cells by inhibiting p53 activity. Mechanistically, RMRP retains SNRPA1 in the nucleus, thus preventing its lysosomal degradation. The nuclear SNRPA1 then prompts MDM2-mediated p53 ubiquitination and degradation. Remarkably, RMRP expression is induced by poly (ADP-ribose) polymerase (PARP) inhibitors, a group of targeted anticancer drugs, through the transcription factor C/EBPβ. Targeting RMRP significantly enhances sensitivity of colorectal cancer cells to PARP inhibition by reactivating p53. Our study provides a possible mechanism underling tumor resistance to PARP inhibitors.