Silencing of lncRNA UCA1 curbs proliferation and accelerates apoptosis by repressing SIRT1 signals by targeting miR-204 in pediatric AML.

Abstract

The long noncoding RNA urothelial carcinoma-associated 1 (UCA1) has been reported to sustain the proliferation of acute myeloid leukemia (AML) cells through downregulating cell cycle regulators p27kip1 . Yet, the foundational mechanism of UCA1 in AML pathologies remains unclear. Herein, we found an escalation of UCA1 expression and suppression of miR-204 expression in pediatric AML patients and cells. UCA1 silencing suppressed cell proliferative abilities, promoted apoptotic rates, decreased Ki67, and increased cleaved caspase-3 in AML cells. Moreover, UCA1 sponged miR-204 and suppressed its expression. UCA1 overexpression inversed the miR-204 suppressed proliferation and promoted apoptosis. UCA1 also boosted the expression of SIRT1, a miR-204 target, via the sponging interaction. Furthermore, miR-204 inhibited inducible nitric oxide synthase and cyclooxygenase-2 expression, while UCA1 overexpression inversed the inhibitory effects in AML cells. Our findings concluded that UCA1 downregulation repressed cell proliferation and promoted apoptosis through inactivating SIRT1 signals by upregulating miR-204 in pediatric AML.

• Authors: Yu Liang, Erwei Li, Hongliang Zhang, Lina Zhang, Yingying Tang, Yuanyuan Wanyan
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 34 Issue 3 Pg. e22435 (Mar 2020) ISSN: 1099-0461 [Electronic] United States
• PMID: 31916649 (Publication Type: Journal Article)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• MIRN204 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• RNA, Long Noncoding
• RNA, Neoplasm
• UCA1 RNA, human
• SIRT1 protein, human
• Sirtuin 1

Topics

• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Child
• Female
• Gene Silencing
• Humans
• Leukemia, Myeloid, Acute (genetics, metabolism, pathology)
• Male
• MicroRNAs (genetics, metabolism)
• Neoplasm Proteins (genetics, metabolism)
• RNA, Long Noncoding (biosynthesis, genetics)
• RNA, Neoplasm (genetics, metabolism)
• Sirtuin 1 (genetics, metabolism)