Title:Circular RNA NF1-419 Inhibits Proliferation and Induces Apoptosis by
Regulating Lipid Metabolism in Astroglioma Cells
Volume: 17
Issue: 2
Author(s): Ran Li, Xiaocui Tang, Changqiong Xu, Yinrui Guo, Longkai Qi, Shan Li, Qiuyun Ren, Wu Jie*Diling Chen*
Affiliation:
- Brain Function and Disease Laboratory, Shantou University Medical College,
No. 22 Xinling Road, Shantou 515041, Guangdong Province, P.R. China
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology
Southern China, Institute of Microbiology, Guangdong Academy of Sciences (Guang Dong Detection Center of Microbiology),
Guangzhou 510070, P.R. China
Keywords:
Circular RNA, circNF1-419, lipid metabolism, apoptosis, U87 astroglioma cell, Ganoderma lucidum.
Abstract:
Background: Astroglioma is the most common primary tumor of the central nervous
system. Currently, there is no effective treatment for astroglioma. In the present study, the extract
(L3) from Ganoderma Lucidum (G. lucidum) was found to inhibit the growth of astroglioma U87
cells and change the expression of circular RNAs (circRNAs). One of these, including the circular
NF1-419 (circNF1-419), was of interest because NF1 gene is a classic tumor suppressor gene.
Objectives: The functional role of circ-NF1-419 in the inhibition of astroglioma cells remains unknown.
This study focuses on the role of circNF1-419 in functional abnormalities of U87 astroglioma
cells and aims to elaborate on its regulatory mechanism.
Methods: The circNF1-419 overexpressing U87 (U87-NF1-419) cells were constructed. We generated
U87-NF1-419 to evaluate the role of circNF1-419 on cell cycle, apoptosis, proliferation, tumor
growth and metabolic regulation. Finally, we used docking screening to identify compounds in
G. lucidum extracts that target circ-419.
Results: U87-NF1-419 can promote cell apoptosis and regulate lipid metabolism through
glycerophospholipid metabolism and retrograde endocannabinoid signaling. Further examinations
revealed that the expression of metabolic regulators, such as L-type voltage-operated calcium channels
(L-VOCC), phospholipase C-β3 (PLCβ3), Mucin1, cationic amino acid transporter 4 (CAT4),
cationic amino acid transporter 1 (CAT1) and a kinase (PRKA) anchor protein 4 (AKAP4) was inhibited,
while phosphatidylserine synthase 1 (PTDSS1) was enhanced in U87-NF1-419 cells. In
vivo experiments showed that circNF1-419 inhibits tumor growth in BALB/C nude mice, and enhanced
AKAP4 and PTDSS1 in tumor tissues. The virtual docking screening results supported that
ganosporeric acid A, ganodermatriol, ganoderic acid B and α-D-Arabinofuranosyladenine in L3
could activate circNF1-419 in astroglioma treatment.
Conclusion: This study indicated that circNF1-419 could be a therapeutic target for the clinical
treatment of astroglioma. L3 from Ganoderma Lucidum (G. lucidum) could inhibit astroglioma
growth by activating circNF1-419.
