CircPOSTN/miR-361-5p/TPX2 axis regulates cell growth, apoptosis and aerobic glycolysis in glioma cells

Niya Long; Liangzhao Chu; Jun Jia; Shuo Peng; Yuan Gao; Hua Yang; Yaoming Yang; Yan Zhao; Jian Liu

doi:10.1186/s12935-020-01454-x

CircPOSTN/miR-361-5p/TPX2 axis regulates cell growth, apoptosis and aerobic glycolysis in glioma cells

Cancer Cell Int. 2020 Aug 6:20:374. doi: 10.1186/s12935-020-01454-x. eCollection 2020.

Authors

Niya Long^#^{1

2

3

4}, Liangzhao Chu^#^{1

4}, Jun Jia^{1

4}, Shuo Peng⁴, Yuan Gao⁴, Hua Yang^{1

4}, Yaoming Yang⁵, Yan Zhao^{2

3}, Jian Liu^{1

2

3

4}

Affiliations

¹ Department of Pathology, Guizhou Medical University, No. 9 Beijing Road, Guiyang, 550004 Guizhou China.
² Key Laboratory of Endemic and Ethnic Diseases, (Guizhou Medical University) Ministry of Education, No. 9 Beijing Road, Guiyang, 550004 Guizhou China.
³ Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, Guizhou 550004 China.
⁴ Department of Neurosurgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou China.
⁵ Department of Biology, Guizhou Medical University, No. 9 Beijing Road, Guiyang, 550004 Guizhou China.

^# Contributed equally.

Abstract

Background: Glioma is the most primary central nervous system tumor in adults. The 5 year survival rate for glioma patients remains poor, although treatment strategies had improved in the past few decades. The cumulative studies have shown that circular RNA (circRNA) is associated with glioma process, so the purpose of this study is to clarify the function of circPOSTN in glioma.

Methods: The expression levels of circPOSTN, miR-361-5p, and targeting protein for Xenopus kinesin-like protein 2 (TPX2) were assessed with real-time quantitative polymerase chain reaction (RT-qPCR). The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays were executed to examine proliferation and apoptosis of glioma cells, respectively. Western blot was applied to assess protein expression. The glucose metabolism of glioma cells was analyzed by testing the glucose consumption, lactate production, ATP level, reactive oxygen species (ROS) accumulation and performing Seahorse XF assay. The interaction relationship between miR-361-5p and circPOSTN or TPX2 was analyzed by bioinformatics database and dual-luciferase reporter assay. The influences of circPOSTN silencing in vivo were observed by a xenograft experiment.

Results: CircPOSTN was overexpressed in glioma tissues and cells. Absence of circPOSTN in glioma cells promoted apoptosis while impeded proliferation and aerobic glycolysis, which were mitigated by silencing miR-361-5p. What's more, loss-of-functional experiment suggested that knockdown of TPX2 repressed proliferation and aerobic glycolysis, while induced apoptosis in glioma cells. In addition, circPOSTN targetedly regulated TPX2 expression in glioma cells via sponging miR-361-5p. In vivo study revealed that deficiency of circPOSTN restrained tumor growth.

Conclusion: Mechanistically, circPOSTN regulated cell growth, apoptosis, and aerobic glycolysis in glioma through miR-361-5p/TPX2 axis.

Keywords: Aerobic glycolysis; Circular RNA; Glioma; TPX2; circPOSTN; miR-361-5p.