TY - JOUR
T1 - Long non-coding RNA TILR constitutively represses TP53 and apoptosis in lung cancer
AU - Iwai, Mika
AU - Kajino, Taisuke
AU - Nakatochi, Masahiro
AU - Yanagisawa, Kiyoshi
AU - Hosono, Yasuyuki
AU - Isomura, Hisanori
AU - Shimada, Yukako
AU - Suzuki, Motoshi
AU - Taguchi, Ayumu
AU - Takahashi, Takashi
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/1/27
Y1 - 2023/1/27
N2 - Non-coding RNAs have an integral regulatory role in numerous functions related to lung cancer development. Here, we report identification of a novel lncRNA, termed TP53-inhibitinglncRNA (TILR), which was found to function as a constitutive negative regulator of p53 expression, including activation of downstream genes such as p21 and MDM2, and induction of apoptosis. A proteomic search for TILR-associated proteins revealed an association with PCBP2, while the mid-portion of TILR was found to be required for both PCBP2 and p53 mRNA binding. In addition, depletion of PCBP2 resulted in phenocopied effects of TILR silencing. TILR was also shown to suppress p53 expression in a post-transcriptional manner, as well as via a positive feedback loop involving p53 and Fanconi anemia pathway genes. Taken together, the present findings clearly demonstrate that TILR constitutively inhibits p53 expression in cooperation with PCBP2, thus maintaining p53 transcriptional activity at a level sufficiently low for avoidance of spurious apoptosis induction.
AB - Non-coding RNAs have an integral regulatory role in numerous functions related to lung cancer development. Here, we report identification of a novel lncRNA, termed TP53-inhibitinglncRNA (TILR), which was found to function as a constitutive negative regulator of p53 expression, including activation of downstream genes such as p21 and MDM2, and induction of apoptosis. A proteomic search for TILR-associated proteins revealed an association with PCBP2, while the mid-portion of TILR was found to be required for both PCBP2 and p53 mRNA binding. In addition, depletion of PCBP2 resulted in phenocopied effects of TILR silencing. TILR was also shown to suppress p53 expression in a post-transcriptional manner, as well as via a positive feedback loop involving p53 and Fanconi anemia pathway genes. Taken together, the present findings clearly demonstrate that TILR constitutively inhibits p53 expression in cooperation with PCBP2, thus maintaining p53 transcriptional activity at a level sufficiently low for avoidance of spurious apoptosis induction.
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U2 - 10.1038/s41388-022-02546-w
DO - 10.1038/s41388-022-02546-w
M3 - Article
C2 - 36522487
AN - SCOPUS:85144081839
SN - 0950-9232
VL - 42
SP - 364
EP - 373
JO - Oncogene
JF - Oncogene
IS - 5
ER -
