Roles of lncRNA LVBU in regulating urea cycle/polyamine synthesis axis to promote colorectal carcinoma progression.
Oncogene
; 41(36): 4231-4243, 2022 09.
Article
in En
| MEDLINE
| ID: mdl-35906392
ABSTRACT
Altered expression of Urea Cycle (UC) enzymes occurs in many tumors, resulting a metabolic hallmark termed as UC dysregulation. Polyamines are synthesized from ornithine, and polyamine synthetic genes are elevated in various tumors. However, the underlying deregulations of UC/ polyamine synthesis in cancer remain elusive. Here, we characterized a hypoxia-induced lncRNA LVBU (lncRNA regulation via BCL6/urea cycle) that is highly expressed in colorectal cancer (CRC) and correlates with poor cancer prognosis. Increased LVBU expression promoted CRC cells proliferation, foci formation and tumorigenesis. Further, LVBU regulates urea cycle and polyamine synthesis through BCL6, a negative regulator of p53. Mechanistically, overexpression of LVBU competitively bound miR-10a/miR-34c to protect BCL6 from miR-10a/34c-mediated degradation, which in turn allows BCL6 to block p53-mediated suppression of genes (arginase1 ARG1, ornithine transcarbamylase OTC, ornithine decarboxylase 1 ODC1) involved in UC/polyamine synthesis. Significantly, ODC1 inhibitor attenuated the growth of patient derived xenografts (PDX) that sustain high LVBU levels. Taken together, elevated LVBU can regulate BCL6-p53 signaling axis for systemic UC/polyamine synthesis reprogramming and confers a predilection toward CRC development. Our data demonstrates that further drug development and clinical evaluation of inhibiting UC/polyamine synthesis are warranted for CRC patients with high expression of LVBU.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
MicroRNAs
/
RNA, Long Noncoding
Limits:
Animals
/
Humans
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2022
Document type:
Article
Affiliation country:
China