Abstract
The altered expression of microRNA (miRNA) has been implicated in glioma. Here, the current study aimed to clarify the oncogenic effects of miR-19b-3p on cellular processes of glioma and to elucidate the underlying mechanism associated with SOCS3 and the JAK-STAT signaling pathway. Differentially expressed genes related to glioma were initially identified via microarray analysis. Twenty-five glioma patients were selected for clinical data collection, while additional 12 patients with traumatic brain injuries were selected as controls. Cell senescence was assessed by β-galactosidase staining, proliferation by MTT assay and apoptosis by flow cytometry following gain- and/or loss-of-function of miR-19b-3p or SOCS3. Glioma xenograft mouse model was developed through subcutaneous injection to nude mice to provide evidence in vivo. The glioma patients exhibited overexpressed miR-19b-3p and poorly-expressed SOCS3. SOCS3 was identified as a target gene of miR-19b-3p through dual-luciferase reporter gene assay. miR-19b-3p repressed SOCS3 expression and activated the JAK-STAT signaling pathway. Furthermore, miR-19b-3p inhibition promoted apoptosis and senescence, and suppressed cell proliferation through inactivation of the JAK-STAT signaling pathway and up-regulation of SOCS3. The reported regulatory axis was validated in nude mice as evidenced by suppressed tumor growth. Taken together, this study demonstrates that miR-19b-3p facilitates glioma progression via activation of the JAK-STAT signaling pathway by targeting SOCS3, highlighting a novel therapeutic target for glioma treatment.
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The data underlying this article will be shared on reasonable request to the corresponding author.
Abbreviations
- miRs:
-
microRNAs
- JAK-STAT:
-
The Janus kinase-signal transducer and activator of transcription
- SOCS :
-
the suppressor of cytokine signaling
- DEGs:
-
differentially expressed genes
- 3’-UTR:
-
3’-untranslated region
- HE:
-
hematoxylin-eosin
- KPS:
-
Karnofsky performance scale
- DMEM:
-
Dulbecco’s modified eagle medium
- PLB:
-
passive lysis buffer
- NC:
-
The negative control
- RT-qPCR:
-
Reverse transcription quantitative polymerase chain reaction
- BSA:
-
bovine serum albumin
- Bax:
-
Bcl-2 Associated X Protein
- OD:
-
optical density
- MT:
-
mutation type
- IHC:
-
Immunohistochemistry
- ANOVA:
-
analysis of variance
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Tao Li conceived and designed research. Hong Ge performed experiments. Qingyan Yang interpreted results of experiments. Junmei Wang analyzed data. Qian Yin prepared figures. Hongbin Wang drafted paper. Gaolei Hou edited and revised manuscript. All authors read and approved final version of manuscript.
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All study protocols were performed with approval from the Ethical Committee of Affiliated Hospital of Hebei Engineering University. Written informed consent was obtained from all patients prior to examination. The animal usage and experiment procedure were approved by the Animal Ethics Committee of the Affiliated Hospital of Hebei Engineering University.
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Li, T., Ge, H., Yang, Q. et al. Oncogenic role of microRNA-19b-3p-mediated SOCS3 in glioma through activation of JAK-STAT pathway. Metab Brain Dis 38, 945–960 (2023). https://doi.org/10.1007/s11011-022-01136-9
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DOI: https://doi.org/10.1007/s11011-022-01136-9