Circular RNA NF1-419 Inhibits Proliferation and Induces Apoptosis by Regulating Lipid Metabolism in Astroglioma Cells

被引：5

作者：

Li, Ran ^{[1
,2
,3
]}

Tang, Xiaocui ^{[4
]}

Xu, Changqiong ^{[3
]}

Guo, Yinrui ^{[1
,4
]}

Qi, Longkai ^{[4
]}

Li, Shan ^{[1
]}

Ren, Qiuyun ^{[3
]}

Jie, Wu ^{[3
]}

Chen, Diling ^{[4
]}

机构：

[1] Hunan Yueyang Maternal & Child Hlth Care Hosp, 693 Baling Middle Rd, Yueyang 414000, Peoples R China

[2] Yueyang Hosp Tradit Chinese Med, 269 Fengqiaohu Rd, Yueyang 414000, Peoples R China

[3] Shantou Univ Med Coll, Brain Funct & Dis Lab, 22 Xinling Rd, Shantou 515041, Guangdong, Peoples R China

[4] Guangdong Acad Sci, Guangdong Prov Key Lab Microbial Safety & Hlth, State Key Lab Appl Microbiol Southern China, Inst Microbiol,Guang Dong Detect Ctr Microbiol, Guangzhou 510070, Peoples R China

来源：

RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY | 2022年 / 17卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Circular RNA; circNF1-419; lipid metabolism; apoptosis; U87 astroglioma cell; Ganoderma lucidum; CHAIN FATTY-ACIDS; GANODERMA-LUCIDUM POLYSACCHARIDES; LONG-CHAIN; PPAR-ALPHA; CANCER; IDENTIFICATION; ACTIVATION; MUSHROOM; CERAMIDE; STRESS;

D O I：

10.2174/1574892816666210729125802

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-ss 3 (PLC ss 3), 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 a-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.

引用

页码：162 / 177

页数：16

共 75 条

[41] CircRNA: functions and properties of a novel potential biomarker for cancer [J].