Dataset Information

Mir-338-3p targeting THBS1 attenuates glioma progression by inhibiting the PI3K/Akt pathway.

ABSTRACT:

Background

Glioma is a brain tumor with high morbidity and mortality rates. Understanding its molecular pathogenesis can provide targets and therapeutic strategies for glioma treatment. miR-338-3p represses tumor growth in several cancers, including glioma. Thus, this study aimed to identify the regulatory effects of miR-338-3p/phosphoinositide 3-kinase (PI3K)/Akt/thrombospondins 1 (THBS1) on glioma progression.

Materials and methods

Quantitative reverse transcription polymerase chain reaction and western blotting were performed to evaluate the levels of miR-338-3p, THBS1, and PI3K/Akt phosphorylation-related proteins. TargetScan software predicted that miR-338-3p targeted THBS1. This was confirmed by performing the dual-luciferase assay. Wound-healing and cell-counting-kit-8 experiments were performed to analyze how THBS1 and miR-338-3p affect the ability of glioma cells to migrate and proliferate. The effect of miR-338-3p on tumorigenicity in mice was also analyzed.

Results

miR-338-3p downregulation was observed in gliomas, whereas THBS1 showed the opposite trend. By suppressing the PI3K/Akt signaling pathway activation, miR-338-3p overregulated the ability of glioma cells to migrate and proliferate in vitro. Additionally, miR-338-3p inhibited the development of glioma tumors in vivo. Moreover, miR-338-3p directly targeted THBS1. THBS1 overexpression promoted glioma cell migration and proliferation by increasing PI3K/Akt phosphorylation. Nonetheless, miR-338-3p overregulation alleviated the effects of THBS1 overexpression.

Conclusion

The miR-338-3p/PI3K/Akt/THBS1 regulatory axis can modulate the progression of glioma cell proliferation and migration; thus, it can be considered a therapeutic biomarker.

SUBMITTER: Jiang L

PROVIDER: S-EPMC10807173 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Mir-338-3p targeting THBS1 attenuates glioma progression by inhibiting the PI3K/Akt pathway.

Jiang Lianglei L Fang Ting T Hu Tingting T Feng Jun J Yan Pengfei P

Biology direct 20240124 1

<h4>Background</h4>Glioma is a brain tumor with high morbidity and mortality rates. Understanding its molecular pathogenesis can provide targets and therapeutic strategies for glioma treatment. miR-338-3p represses tumor growth in several cancers, including glioma. Thus, this study aimed to identify the regulatory effects of miR-338-3p/phosphoinositide 3-kinase (PI3K)/Akt/thrombospondins 1 (THBS1) on glioma progression.<h4>Materials and methods</h4>Quantitative reverse transcription polymerase c ...[more]

PMID: 38267974

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Project description:ObjectiveCasticin is generally used in traditional herbal medicine for its anti-inflammatory and anticarcinogenic pharmacological properties. Also, microRNAs are indispensable oncogenes or cancer suppressors being dysregulated in various diseases. In this study, we aimed to elucidate the mechanisms underlying effects of casticin on the progression of acute myeloid leukemia (AML).MethodsCCK-8 and flow cytometry were utilized to measure the proliferation and apoptosis of AML cell lines, respectively, after treatment with different concentrations of casticin. The alteration of several microRNA expressions in response to casticin treatment was detected by performing qRT-PCR, and the activity of PI3K/Akt pathways was evaluated through immunoblotting. Afterwards, the potential target gene of miR-338-3p was investigated by dual-luciferase reporter assay. In order to evaluate the role of miR-338-3p in the casticin-induced cellular phenotype changes, AML cells were transfected with miR-338-3p mimics or inhibitor and then subjected to proliferation and apoptosis analysis. Finally, a mouse xenograft model system was employed to investigate the role of casticin in AML progression in vivo.ResultsSuppressed cellular proliferation and enhanced apoptosis were observed in HL-60 and THP-1 cells after exposure to casticin, accompanied by remarkable upregulation of the miR-338-3p expression as well as a decline in the phosphorylation of PI3K and Akt proteins. RUNX2 was identified as a direct target molecular of miR-338-3p, which might account for the findings that miR-338-3p knockdown enhanced the PI3K/Akt pathway activity, whereas the miR-338-3p overexpression inactivated this signaling pathway. In addition, the inhibition of the miR-338-3p expression attenuated severe cell apoptosis and suppressions of PI3K/Akt pathway induced by casticin. Furthermore, casticin treatment retarded tumor growth rate in mouse models, whilst elevating miR-338 expression and repressing the activity of PI3K/Akt pathway in vivo. However, miR-338-3p depletion could also abolish the phenotypic alterations caused by casticin treatment.ConclusionCasticin promotes AML cell apoptosis but inhibits AML cell proliferation in vitro and tumor growth in vivo by upregulating miR-338-3p, which targets RUNX2 and thereafter inactivates PI3K-Akt signaling pathway. Our results provide insights into the mechanisms underlying the action of casticin in the control of AML progression.

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Dataset Information

Mir-338-3p targeting THBS1 attenuates glioma progression by inhibiting the PI3K/Akt pathway.

Background

Materials and methods

Results

Conclusion

Publications

Mir-338-3p targeting THBS1 attenuates glioma progression by inhibiting the PI3K/Akt pathway.

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